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BACKGROUND: Previous studies found an association between osteoarthritis (OA) and risk of cardiovascular disease (CVD) and therefore suggested intensive treatment of cardiovascular risk factors in OA patients. However, prospective population-based data is lacking. OBJECTIVES: To investigate the association between OA and CVD longitudinally in a general population and examine the role of disability in this association. METHODS: This study was embedded in the Rotterdam Study, a prospective population-based cohort study in Rotterdam, the Netherlands that started in 1989. At baseline 4648 persons aged ≥55, free of CVD were classified into those with and those without radiographic or clinical OA. HRs adjusted for traditional cardiovascular risk factors for developing CVD (a composite of fatal and non-fatal coronary heart disease and stroke) were calculated. RESULTS: During a median follow-up of 14.4â years, 1230 cardiovascular events occurred, of which 101 were in participants with clinical OA. Presence of radiographic OA at baseline was not related to future CVD (HR 0.99, 95% CI 0.86 to 1.15), neither was presence of clinical OA (HR 1.09, 95% CI 0.88 to 1.34). However, persons with increasing disability were more likely to suffer a cardiovascular event compared with non-disabled persons (HR 1.26, 95% CI 1.12 to 1.42); this was independent of the presence of OA. CONCLUSIONS: In this large population-based study, participants with OA were not at increased risk of CVD. The close relation between disability and osteoarthritis may explain previous findings. Further studies are required in order to clarify whether OA patients need more intensive treatment of their cardiovascular risk factors.
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Actividades Cotidianas , Enfermedad Coronaria/epidemiología , Personas con Discapacidad/estadística & datos numéricos , Osteoartritis/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Osteoartritis/diagnóstico por imagen , Osteoartritis/fisiopatología , Estudios Prospectivos , Radiografía , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids. DESIGN AND METHODS: We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800). RESULTS: After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed. CONCLUSION: Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.
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Población Negra , Ácidos Grasos/metabolismo , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad , Obesidad/genética , Polimorfismo de Nucleótido Simple , Población Blanca , Tejido Adiposo , Adulto , Anciano , Anciano de 80 o más Años , Población Negra/genética , Índice de Masa Corporal , Europa (Continente)/epidemiología , Femenino , Frecuencia de los Genes , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Fenotipo , Prevalencia , Estados Unidos/epidemiología , Población Blanca/genéticaRESUMEN
Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).
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Moléculas de Adhesión Celular/genética , Café/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A2/genética , Ingestión de Líquidos/genética , Estudio de Asociación del Genoma Completo/métodos , Antígenos de Neoplasias/genética , Proteínas Reguladoras de la Apoptosis/genética , Cafeína/farmacología , Línea Celular , Femenino , Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Proteínas Serina-Treonina Quinasas/genética , Población Blanca/genéticaRESUMEN
AIMS/HYPOTHESIS: An APOC3 promoter haplotype has been previously associated with type 1 diabetes. In this population-based study, we investigated whether APOC3 polymorphisms increase type 2 diabetes risk and need for insulin treatment in lean participants. METHODS: In the Rotterdam Study, a population-based prospective cohort (n = 7,983), Cox and logistic regression models were used to analyse the associations and interactive effects of APOC3 promoter variants (-482C > T, -455T > C) and BMI on type 2 diabetes risk and insulin treatment. Analyses were followed by replication in an independent case-control sample (1,817 cases, 2,292 controls) and meta-analysis. RESULTS: In lean participants, the -482T allele was associated with increased risk of prevalent and incident type 2 diabetes: OR -482CT 1.47 (95% CI 1.13-1.92), -482TT 1.40 (95% CI 0.83-2.35), p = 0.009 for trend; HR -482CT 1.35 (95% CI 0.96-1.89), -482TT 1.68 (95% CI 0.91-3.1), p = 0.03 for trend, respectively. These results were confirmed by replication. Meta-analysis was highly significant (-482T meta-analysis p = 1.1 × 10(-4)). A borderline significant interaction was observed for insulin use among participants with type 2 diabetes (-482CT*BMI p = 0.06, -455TC*BMI p = 0.02). CONCLUSIONS/INTERPRETATION: At a population-based level, the influence of APOC3 promoter variants on type 2 diabetes risk varies with the level of adiposity. Lean carriers of the -482T allele had increased type 2 diabetes risk, while such an effect was not observed in overweight participants. Conversely, in overweight participants the -455C allele seemed protective against type 2 diabetes. The interaction of the variants with need for insulin treatment may indicate beta cell involvement in lean participants. Our findings suggest overlap in the genetic backgrounds of type 1 diabetes and type 2 diabetes in lean patients.
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Apolipoproteína C-III/genética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad/genética , Insulina/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Delgadez/fisiopatología , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Estudios de Cohortes , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Haplotipos , Humanos , Hipoglucemiantes/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Países Bajos , Prevalencia , Regiones Promotoras Genéticas/genética , Estudios Prospectivos , Factores de RiesgoRESUMEN
The objective of this study was to investigate whether common variation in genes involved in lipid metabolism modify the effect of statins on serum total cholesterol concentration. Statin users were identified in the Rotterdam Study, a prospective population-based cohort study of subjects >55 years of age. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in lipid metabolism and total cholesterol response to statin therapy, using linear regression analysis and adjusting for potential confounders. Replication was performed in an independent extended cohort of the Rotterdam Study. Genotype data and total cholesterol concentrations after start of statin therapy were available for 554 newly started statin users. Two SNPs were associated with a significantly higher cholesterol concentration under statin therapy: SNP rs1532624 in the CETP gene (ß: 0.141 mmol l(-1), P=0.004 per additional allele) and SNP rs533556 in the APOA1 gene (ß: 0.138 mmol l(-1), P=0.005 per additional allele). In the replication sample, only the CETP rs1532624 SNP again showed a significant association. The SNPs were not related to baseline total cholesterol in non-statin users. In conclusion, we found that the CETP rs1532624 polymorphism is associated with cholesterol response to statin therapy in a cohort of elderly subjects in the general population.
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Colesterol/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Metabolismo de los Lípidos/genética , Polimorfismo de Nucleótido Simple , Anciano , Estudios de Cohortes , Femenino , Variación Genética , Genotipo , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Patients with heart failure used to have an increased risk of stroke, but this may have changed with current treatment regimens. We assessed the association between heart failure and the risk of stroke in a population-based cohort that was followed since 1990. The study uses the cohort of the Rotterdam Study and is based on 7,546 participants who at baseline (19901993) were aged 55 years or over and free from stroke. The associations between heart failure and risk of stroke were assessed using time-dependent Cox proportional hazards models, adjusted for cardiovascular risk factors (smoking, diabetes mellitus, BMI, ankle brachial index, blood pressure, atrial fibrillation, myocardial infarction and relevant medication). At baseline, 233 participants had heart failure. During an average follow-up time of 9.7 years, 1,014 persons developed heart failure, and 827 strokes (470 ischemic, 75 hemorrhagic, 282 unclassified) occurred. The risk of ischemic stroke was more than five-fold increased in the first month after diagnosis of heart failure (age and sex adjusted HR 5.79, 95% CI 2.1515.62), but attenuated over time (age and sex adjusted HR 3.50 [95% CI 1.966.25] after 16 months and 0.83 [95% CI 0.531.29] after 0.56 years). Additional adjustment for cardiovascular risk factors only marginally attenuated these risks. In conclusion, the risk of ischemic stroke is strongly increased shortly after the diagnosis of heart failure but returns to normal within 6 months after onset of heart failure.
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Insuficiencia Cardíaca/complicaciones , Accidente Cerebrovascular/epidemiología , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Accidente Cerebrovascular/etiologíaRESUMEN
While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)-levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women.
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Trastornos del Conocimiento/genética , Función Ejecutiva/fisiología , Síndrome Metabólico/genética , Adiponectina/sangre , Adiponectina/genética , Adiponectina/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Proteína C-Reactiva/genética , Proteína C-Reactiva/fisiología , Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/etiología , Estudios de Cohortes , Estudios Transversales , Familia , Femenino , Humanos , Resistencia a la Insulina/genética , Resistencia a la Insulina/fisiología , Modelos Lineales , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Países Bajos , Factores Sexuales , Adulto JovenRESUMEN
OBJECTIVE: Besides effects on hemostasis, vitamin K-dependent proteins play a role in bone mineralization and arterial calcification. We investigated the association between the VKORC1 1173C>T polymorphism and calcification of the aortic far wall in a large population-based cohort. METHODS AND RESULTS: Aortic calcification was diagnosed by radiographic detection of calcified deposits in the abdominal aorta. In all cohort members for whom DNA was available, the C1173T SNP of VKORC1 (rs9934438) was determined. With multivariable logistic regression analysis the association between this polymorphism and the risk of aortic calcification was calculated, adjusted for potential confounders. The T allele frequency of the VKORC1 1173C>T polymorphism was 38.8%. 1185 (37.2%) persons were homozygous CC, 1529 (48,0%) were heterozygous CT and 473 (14.8%) were homozygous TT. Persons with at least one T-allele had a statistically significant 19% (95% CI 2 to 40%) risk increase of calcification of the aortic far wall compared to CC homozygous persons, adjusted for age and gender. CONCLUSIONS: The T-allele of the VKORC1 1173C>T polymorphism was associated with a significantly higher risk of aortic calcification in Whites.
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Enfermedades de la Aorta/enzimología , Enfermedades de la Aorta/genética , Calcinosis/enzimología , Calcinosis/genética , Oxigenasas de Función Mixta/genética , Polimorfismo de Nucleótido Simple , Anciano , Alelos , Aorta Abdominal , Enfermedades de la Aorta/etiología , Calcinosis/etiología , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Estudios Prospectivos , Factores de Riesgo , Vitamina K Epóxido ReductasasRESUMEN
OBJECTIVE: We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. DESIGN: Population-based birth cohort study. SETTING: Data of pregnant women and their children in Rotterdam, the Netherlands. POPULATION: In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. METHODS: Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. MAIN OUTCOME MEASURES: Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. RESULTS: Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size (P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. CONCLUSIONS: Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined.
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Índice de Masa Corporal , Desarrollo Fetal/fisiología , Aumento de Peso/fisiología , Adulto , Femenino , Peso Fetal/fisiología , Edad Gestacional , Humanos , Recién Nacido , Países Bajos , Embarazo , Resultado del Embarazo , Trimestres del EmbarazoRESUMEN
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided by the level of blood pressure. In the secondary prevention setting, there are no means of guiding therapy. Prior attempts to target ACE-inhibitors to those patients that are most likely to benefit have not been successful, mainly due to the consistency in the treatment effect in clinical subgroups. Still, for prolonged prophylactic treatment with ACE-inhibitors it would be best to target treatment to only those patients most likely to benefit, which would considerably lower the number needed to treat and increase cost-effectiveness. A new approach for such "tailored-therapy" may be to integrate information on the genetic variation between patients. Until now, pharmacogenetic research of the efficacy of ACE-inhibitor therapy in CAD patients is still in a preliminary stage. METHODS: The PERindopril GENEtic association study (PERGENE) is a substudy of the EUROPA trial, a randomized double-blind placebo-controlled multicentre clinical trial which demonstrated a beneficial effect of the ACE-inhibitor perindopril in reducing cardiovascular morbidity and mortality in 12.218 patients with stable coronary artery disease (mean follow-up 4.2 years). Blood tubes were received from patients at the beginning of the EUROPA trial and buffy coats were stored at -40 degrees C at the central core laboratory. Candidate genes were selected in the renin-angiotensin-system and bradykinin pathways. Polymorphisms were selected based on haplotype tagging principles using the HapMap genome project, Seattle and other up-to-date genetic database platforms to comprehensively cover all common genetic variation within the genes. Selection also took into consideration the functionality of SNP's, location within the gene (promoter) and existing relevant literature. The main outcome measure of PERGENE is the effect of genetic factors on the treatment benefit with ACE-inhibitors. The size of this pharmacogenetic substudy allows detection with a statistical power of 98% to detect a difference in hazard ratios (treatment effect) of 20% between genotypes with minor allele frequency of 0.20 (two-sided alpha 0.05). CONCLUSION: The PERGENE study is a large cardiovascular pharmacogenetic study aimed to assess the feasibility of pharmacogenetic profiling of the treatment effect of ACE-inhibitor use with the perspective to individualize treatment in patients with stable coronary artery disease.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Perindopril/farmacología , Farmacogenética , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Enfermedad de la Arteria Coronaria/genética , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal axis has been suggested as an independent risk factor for ischemic heart disease. The aim of our study was to evaluate whether two markers of the hypothalamic-pituitary-adrenal axis activity, the level of salivary cortisol and the diurnal salivary cortisol pattern, are associated with atherosclerosis of the carotid arteries in an elderly population. METHODS AND RESULTS: A total of 1866 participants of the Rotterdam Study, a population-based cohort study in the elderly, provided four salivary cortisol samples throughout 1 d, and underwent ultrasonography to examine the presence of plaques in the common, internal, and bifurcation sites of both carotid arteries. Two summary measures of the separate cortisol values were computed: area under the curve (AUC), which is a measure of total cortisol exposure while awake; and the slope, which is a measure of diurnal cortisol decline. RESULTS: Total cortisol exposure while awake (AUC) was associated with higher plaque scores (beta = 0.08 per sd of AUC, 95% confidence interval 0.00-0.16; P = 0.04) in a fully adjusted linear regression model. Persons with an AUC in the highest tertile had a higher number of plaques of carotid arteries compared with those in the lowest tertile (3.08 vs. 2.80, 95% confidence interval of difference 0.09-0.48; P = 0.005). There was no relation between diurnal cortisol decline and plaque score. CONCLUSION: Our results support the hypothesis that increased total cortisol exposure is independently associated with atherosclerosis of the carotid arteries.
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Aterosclerosis/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Hidrocortisona/análisis , Saliva/química , Anciano , Anciano de 80 o más Años , Aterosclerosis/epidemiología , Aterosclerosis/patología , Aterosclerosis/fisiopatología , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/fisiopatología , Ritmo Circadiano , Estudios de Cohortes , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/fisiología , Ultrasonografía , Vigilia/fisiologíaRESUMEN
OBJECTIVE: The epidemiological evidence for the association between sleep duration and obesity in the elderly is inconsistent and has not been investigated with objective measures. Furthermore, the role of sleep fragmentation in this relationship is unknown. Our aim was to investigate the association of sleep measures with body mass index (BMI) and obesity in a normal elderly population. DESIGN: Cross-sectional study. SUBJECTS: A total of 983 community-dwelling elderly (mean age 68.4+/-6.9 years, range, 57-97). MEASUREMENTS: Weight and height were measured, and sleep duration and fragmentation were assessed with on average six nights of actigraphy. RESULTS: A quadratic model adequately described the association between continuous measures of sleep duration and BMI. Actigraphic sleep duration had a significant U-shaped relationship with BMI (beta of quadratic term=0.30, 95% confidence interval (CI): 0.08, 0.52). Both short sleepers (<5 h: OR, 2.76 (95% CI: 1.38, 5.49), 5 to <6 h: OR, 1.97 (95% CI: 1.26, 3.08)) and long sleepers (>or=8 h: OR, 2.93 (95% CI: 1.39, 6.16)) were more likely to be obese, compared to participants who slept 7 to <8 h. BMI increased with 0.59 kg m(-2) per standard deviation of sleep fragmentation (95% CI: 0.34, 0.84). After adjustment for sleep fragmentation, the association between short sleep and obesity was no longer significant. Exclusion of participants with probable sleep apnea only marginally changed these associations. Self-reported habitual sleep duration was not associated with BMI or obesity. CONCLUSIONS: Sleep duration, as measured with actigraphy, had a U-shaped relationship with BMI and obesity in an elderly population. A highly fragmented sleep is associated with a higher BMI and a higher risk of obesity, and may explain why short sleep is related to obesity. To preclude bias that can be introduced by self-report measures of sleep duration, using multiple measures of sleep parameters is recommended in future research.
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Índice de Masa Corporal , Obesidad/etiología , Privación de Sueño/complicaciones , Anciano , Anciano de 80 o más Años , Estatura , Peso Corporal , Estudios Transversales , Femenino , Humanos , Estilo de Vida , Modelos Lineales , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Oportunidad Relativa , Riesgo , Privación de Sueño/fisiopatologíaRESUMEN
OBJECTIVES: To examine the development and tracking of subcutaneous fat mass in the first 2 years of life and to examine which parental, fetal and postnatal characteristics are associated with subcutaneous fat mass. DESIGN: This study was embedded in the Generation R Study, a prospective cohort study from early fetal life onward. Subcutaneous fat mass was measured by skinfold thickness (biceps, triceps, suprailiacal, subscapular) at the ages of 1.5, 6 and 24 months in 1012 children. Information about parental, fetal and postnatal growth characteristics was collected by physical and fetal ultrasound examinations and questionnaires. RESULTS: Normal values of subcutaneous fat mass are presented. Total subcutaneous fat mass was higher in girls than in boys at the age of 24 months (P=0.01). Subjects in the lowest and highest quartiles at the age of 6 months tended to keep their position in the same quartile at the age of 24 months (odds ratios 1.86 (95% confidence interval (CI) 1.3, 2.7)) and 1.84 (95% CI: 1.3, 2.6), respectively). Maternal height and weight, paternal weight, fetal weight at 30 weeks, birth weight and weight at the age of 6 weeks were each inversely associated with subcutaneous fat mass at the age of 24 months after adjustment for current weight at 24 months. CONCLUSION: This study shows for the first time that subcutaneous fat mass tends to track in the first 2 years of life. Furthermore, the results suggest that an adverse fetal environment and growth are associated with increased subcutaneous fat mass at the age of 24 months. Further studies are needed to examine whether these associations persist in later life.
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Grosor de los Pliegues Cutáneos , Grasa Subcutánea/anatomía & histología , Tamaño Corporal , Lactancia Materna , Distribución de Chi-Cuadrado , Preescolar , Femenino , Peso Fetal , Encuestas Epidemiológicas , Humanos , Lactante , Alimentos Infantiles , Recién Nacido , Modelos Logísticos , Estudios Longitudinales , Masculino , Edad Materna , Países Bajos , Embarazo , Factores Sexuales , Fumar , Clase SocialRESUMEN
This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or beta-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug-gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model. The risk of MI was reduced in current users of ACE inhibitors with the AGTR1 573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype (synergy index (SI):0.32; 95% confidence interval (CI): 0.14-0.70). No significant drug-gene interaction was found on the risk of stroke (SI:0.82; 95% CI: 0.44-1.52) or in beta-blocker users. Also, no significant drug-gene interaction was found with the ACE I/D polymorphism. In conclusion, subjects with at least one copy of the AGTR1 573C allele might have more benefit from ACE inhibitor therapy.
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Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Infarto del Miocardio/genética , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Accidente Cerebrovascular/genética , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Factores de Riesgo , Accidente Cerebrovascular/prevención & controlRESUMEN
Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3' UTR. The potential existence of another functional polymorphism in the 5' UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.
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Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , HumanosRESUMEN
OBJECTIVE: The 'vascular depression' hypothesis suggests that late-life depression results from vascular brain damage. We studied the longitudinal association between cerebrovascular risk factors and incident depression in a large population-based study. METHOD: Two thousand nine hundred and thirty-one persons with the age of > or =61 years were followed up. Data on a comprehensive set of cerebrovascular risk factors were collected at baseline. Participants received a psychiatric assessment 5 years later to establish DSM-IV diagnoses. RESULTS: Only current smoking and antihypertensive drug use were independently associated with incident depressive symptoms. Diabetes mellitus and the Framingham stroke risk score were related to incident depressive disorder. No relation with depression was observed for cholesterol, diastolic and systolic blood pressure, history of cardiovascular disease, atrial fibrillation, left ventricular hypertrophy or the use of statins and anticoagulants. CONCLUSION: These results moderately support the 'vascular depression' hypothesis.
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Envejecimiento/psicología , Trastornos Cerebrovasculares/epidemiología , Trastorno Depresivo/epidemiología , Características de la Residencia , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/epidemiología , Fibrilación Atrial/psicología , Trastornos Cerebrovasculares/psicología , Colesterol/sangre , Estudios de Cohortes , Comorbilidad , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Diabetes Mellitus/embriología , Diabetes Mellitus/psicología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/psicología , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Fumar/efectos adversosRESUMEN
OBJECTIVES: Correct assessment of gestational age and fetal growth is essential for optimal obstetric management. The objectives of this study were, first, to develop charts for ultrasound dating of pregnancy based on crown-rump length and biparietal diameter and, second, to derive reference curves for normal fetal growth based on biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference and femur length from 10 weeks of gestational age onwards. METHODS: A total of 8313 pregnant women were included for analysis in this population-based prospective cohort study. All women had repeated ultrasound assessments to examine fetal growth. RESULTS: Charts for ultrasound dating of pregnancy, based on crown-rump length and biparietal diameter, were derived. Internal validation with the actual date of delivery showed that ultrasound imaging provided reliable gestational age estimates. Up to 92% of deliveries took place within 37-42 weeks of gestation if gestational age was derived from ultrasound data, compared with 87% based on a reliable last menstrual period. The earlier the ultrasound assessment the more accurate the prediction of date of delivery. After 24 weeks of gestation a reliable last menstrual period provided better estimates of gestational age. Reference curves for normal fetal growth from 10 weeks of gestational age onwards were derived. CONCLUSIONS: Charts for ultrasound dating of pregnancy and reference curves for fetal biometry are presented. The results indicate that, up to 24 weeks of pregnancy, dating by ultrasound examination provides a better prediction of the date of delivery than does last menstrual period. The earlier the ultrasound assessment in pregnancy, preferably between 10 and 12 weeks, the better the estimate of gestational age.
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Desarrollo Fetal , Edad Gestacional , Ultrasonografía Prenatal/métodos , Abdomen/diagnóstico por imagen , Abdomen/embriología , Adulto , Cerebelo/diagnóstico por imagen , Cerebelo/embriología , Largo Cráneo-Cadera , Femenino , Feto/anatomía & histología , Cabeza/diagnóstico por imagen , Cabeza/embriología , Humanos , Estudios Longitudinales , Embarazo , Estudios Prospectivos , Valores de ReferenciaRESUMEN
The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene may be involved in determining blood pressure changes. The aim of the present study was to assess the relationship between the ACE I/D gene and the change of blood pressure levels during follow-up. We calculated the difference between mean levels of SBP, DBP and PP obtained during the two observations as follows: BP mean levels obtained at third phase minus the BP mean levels at baseline and subsequently we investigated the association of the ACE I/D polymorphism and the mean changes of SBP, DBP and PP levels. The study was conducted within the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. Information on the II, ID and DD genotypes of the ACE gene and mean change of blood pressure levels were available in 3966 subjects. In adjusted models, subjects with the D allele had higher mean changes of systolic and pulse pressure (PP) than subjects with the I allele. The mean changes of systolic blood pressure were 6.1 (4.7-7.5), 8.2 (7.5-9.3) and 7.4 (5.9-8.5) mm Hg in subjects with the II, ID and DD genotype, respectively. The corresponding mean changes of PP through genotypes were 4.3 (3.3-5.4), 6.0 (5.3-6.7) and 5.9 (4.9-6.9) mm Hg, respectively. No difference was found for mean change of diastolic blood pressure among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with increased mean changes of systolic and PP.
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Presión Sanguínea , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Anciano , Femenino , Eliminación de Gen , Genotipo , Humanos , Masculino , Mutagénesis InsercionalRESUMEN
Arterial stiffness is a risk factor for cardiovascular disease. Transforming growth factor beta1 is a pleiotropic cytokine, with many functions, including influence on the vascular wall (e.g., on angiogenesis, endothelial cells and the extracellular matrix). We investigated five functional polymorphisms in the transforming growth factor beta1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro and codon 263 Thr/Ile) in relation to arterial stiffness in a population-based study. A total of 3863 participants of the Rotterdam Study, a prospective population-based study, were included in the current study. The relations of the genotypes and haplotypes with arterial stiffness (pulse wave velocity (PWV), distensibility coefficient (DC) and pulse pressure (PP)) were studied using analyses of variance and linear regression. The analyses were adjusted for age, sex, mean arterial pressure, heart rate, conventional cardiovascular risk factors and measures of atherosclerosis. There were no associations between PWV and -800 G/A (P=0.56), -509 C/T (P=0.29), codon 10 (P=0.98) and, codon 25 (P=0.28). These polymorphisms were not associated with the DC or with PP. The haplotype-based analyses yielded similar results. The results of this study show that the TGF-beta1 -800 G/A, -509 C/T, codon 10 Leu/Pro and codon 25 Arg/Pro polymorphisms are not associated with arterial stiffness.
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Arterias/fisiopatología , Polimorfismo Genético , Factor de Crecimiento Transformador beta1/genética , Anciano , Presión Sanguínea , Estudios de Cohortes , Elasticidad , Femenino , Genotipo , Humanos , Masculino , Países Bajos , Estudios Prospectivos , Pulso ArterialRESUMEN
OBJECTIVE: To examine whether differences in birthweight of various ethnic groups residing in The Netherlands can be explained by determinants of birthweight. DESIGN: Population-based birth cohort study. SETTING: Data of pregnant women and their partners in Rotterdam, The Netherlands. POPULATION: We examined data of 6044 pregnant women with a Dutch, Moroccan, Turkish, Capeverdean, Antillean, Surinamese-Creole, Surinamese-Hindustani and Surinamese-other ethnic background. METHODS: Regression analyses were used to assess the impact of biomedical, socio-demographic and lifestyle-related determinants on birthweight differences. MAIN OUTCOME MEASURE: Birthweight was established immediately after delivery in grams. RESULTS: Compared with mean birthweight of offspring of Dutch women (3485 g, SD 555), the mean birthweight was lower in all non-Dutch populations, except in Moroccans. Differences ranged from an 88-g lower birthweight in offspring of the Turkish women to a 424-g lower birthweight in offspring of Surinamese-Hindustani women. Differences in gestational age, maternal and paternal height largely explained the lower birthweight in the Turkish, Antillean, Surinamese-Creole and Surinamese-other populations. Differences in birthweight between the Dutch and the Capeverdean and Surinamese-Hindustani populations could only partly be explained by the studied determinants. CONCLUSIONS: These results confirm significant differences in birthweight between ethnic populations that can only partly be understood from established determinants of birthweight. The part that is understood points to the importance of determinants that cannot easily be modified, such as parental height. Further study is necessary to obtain a fuller understanding.