[show abstract][hide abstract] ABSTRACT: Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1-40 and Aβ1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10-5). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1-42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.
[show abstract][hide abstract] ABSTRACT: Objective:Fetal smoke exposure may influence growth and body composition later life. We examined the associations of maternal and paternal smoking during pregnancy with total and abdominal fat distribution in school-age children.Methods:We performed a population-based prospective cohort study among 5,243 children followed from early pregnancy onwards in the Netherlands. Information about parental smoking was obtained by questionnaires during pregnancy. At the median age of 6.0 years (90% range 5.7-7.4), we measured anthropometrics, total fat and android/gynoid fat ratio by Dual-energy X-ray absorptiometry, and preperitoneal and subcutaneous abdominal fat measured by ultrasound.Results:The associations of maternal smoking during pregnancy were only present among girls (P-value for sex interaction<0.05). Compared to girls from mothers who did not smoke during pregnancy, those from mothers who smoked during the first trimester only had a higher android/gynoid fat ratio (difference 0.23 (95% Confidence Interval (CI) 0.09-0.37) standard deviation scores (SDS). Girls from mothers who continued smoking throughout pregnancy had a higher body mass index (difference 0.24 (95% CI 0.14-0.35) SDS), total fat mass (difference 0.23 (95% CI 0.14-0.33) SDS), android/gynoid fat ratio (difference 0.34 (95% CI 0.22-0.46) SDS), subcutaneous abdominal fat (difference 0.22 (95% CI 0.11-0.33) SDS), and preperitoneal abdominal fat (difference 0.20 (95% CI 0.08-0.31) SDS). Similar associations with body fat distribution outcomes were observed for paternal smoking during pregnancy. Both continued maternal and paternal smoking during pregnancy may be associated with an increased risk of childhood overweight. The corresponding odds ratios were 1.19 (95% CI 0.98-1.46) and 1.32 (1.10-1.58), respectively.Conclusions:Maternal and paternal smoking during pregnancy are associated with an adverse body and abdominal fat distribution and increased risk of overweight in children. Similar effects of maternal and paternal smoking suggest that direct intrauterine mechanisms and common family based lifestyle-related factors explain the associations.International Journal of Obesity accepted article preview online, 22 January 2014. doi:10.1038/ijo.2014.9.
International journal of obesity (2005) 01/2014; · 5.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
To investigate the association between OA and CVD longitudinally in a general population and examine the role of disability in this association.
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.
During a median follow-up of 14.4 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.
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.
Annals of the rheumatic diseases 01/2014; · 8.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate fertility treatment, twin births, and unplanned pregnancies in pregnant women with eating disorders in a population-based sample.
A longitudinal population-based birth cohort (Generation R).
Rotterdam, the Netherlands.
Women from the Generation R study who reported a history of (recent or past) anorexia nervosa (n = 160), bulimia nervosa (n = 265), or both (n = 130), and a history of psychiatric disorders other than eating disorders (n = 1396) were compared with women without psychiatric disorders (n = 4367).
Women were compared on the studied outcomes using logistic regression. We performed crude and adjusted analyses (adjusting for relevant confounding factors).
Fertility treatment, twin births, unplanned pregnancies, and women's feelings towards unplanned pregnancies.
Relative to women without psychiatric disorders, women with bulimia nervosa had increased odds (odds ratio, OR, 2.3; 95% confidence interval, 95% CI, 1.1-5.2) of having undergone fertility treatment. Women with all eating disorders had increased odds of twin births (anorexia nervosa, OR 2.7, 95% CI 1.0-7.7; bulimia nervosa, OR 2.7, 95% CI 1.1-6.6; anorexia and bulimia nervosa, OR 3.795% CI 1.3-10.7). Anorexia nervosa was associated with increased odds of unplanned pregnancies (OR 1.8, 95% CI 1.2-2.6) and mixed feelings about these pregnancies (adjusted OR 5.0, 95% CI 1.7-14.4). Pre-pregnancy body mass index did not explain the observed associations.
Eating disorders are associated with increased odds of receiving fertility treatment and twin births. Women with anorexia nervosa were more likely to have an unplanned pregnancy and have mixed feelings about the unplanned pregnancy. Fertility treatment specialists should be aware that both active and past eating disorders (both anorexia nervosa and bulimia nervosa) might underlie fertility problems.
BJOG An International Journal of Obstetrics & Gynaecology 10/2013; · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: To develop and validate a prognostic model for incident knee osteoarthritis (KOA) in a general population and determine the value of different risk factor groups to prediction.
The prognostic model was developed in 2628 individuals from the Rotterdam Study-I (RS-I). Univariate and multivariate analyses were performed for questionnaire/easily obtainable variables, imaging variables, genetic and biochemical markers. The extended multivariate model was tested on discrimination (receiver operating characteristic curve and area under the curve (AUC)) in two other population-based cohorts: Rotterdam Study-II and Chingford Study.
In RS-I, there was moderate predictive value for incident KOA based on the genetic score alone in subjects aged <65 years (AUC 0.65), while it was only 0.55 for subjects aged ≥65 years. The AUC for gender, age and body mass index (BMI) in prediction for KOA was 0.66. Addition of the questionnaire variables, genetic score or biochemical marker urinary C-terminal cross-linked telopeptide of type II collagen to the model did not change the AUC. However, when adding the knee baseline KL score to the model the AUC increased to 0.79. Applying external validation, similar results were observed in the Rotterdam Study-II and the Chingford Study.
Easy obtainable 'Questionnaire' variables, genetic markers, OA at other joint sites and biochemical markers add only modestly to the prediction of KOA incidence using age, gender and BMI in an elderly population. Doubtful minor radiographic degenerative features in the knee, however, are a very strong predictor of future KOA. This is an important finding, as many radiologists do not report minor degenerative changes in the knee.
Annals of the rheumatic diseases 08/2013; · 8.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background:The ability to taste 6-n-propylthiouracil (PROP) may be associated with body composition, but previous findings from observational studies are conflicting and cannot be interpreted causally. The aim of this study was to estimate the causal association between PROP taster status and body composition in a population-based cohort study.Methods:The study was embedded in a population-based prospective birth cohort study. TAS2R38 genotype (rs713598) was used as an instrumental variable (IV) to obtain unbiased effect estimates of the relation between PROP taster status and body weight (n=3778). Adiposity measures included body mass index and fat mass measured by DXA scan at the child's age of 6 years. Associations were investigated using both ordinary linear regression (OLS) and two-stage least squares regression (2SLS).Results:Non-taster girls had higher BMI standard deviation scores (SDS) and higher body fat as compared to taster girls (results from linear regression BMI SDS: -0.09, P=0.023, body fat mass (%): -0.49, P=0.028). TAS2R38 genotype predicted PROP phenotype (F=240), indicating a strong IV. The 2SLS effect estimates were imprecise but similar to the observational estimates (-0.08 for BMI SDS and -0.46 for body fat mass %) and were not significantly different from the OLS results (Hausman test: P>0.10). For boys there were no differences observed between tasters and non-tasters.Conclusions:Our findings suggest a causal relation between PROP taster status and body weight among 6 year-old girls; Mendelian Randomization were consistent with conventional estimates. In contrast, body weight among boys appeared to be independent of PROP taster status. Further research should focus on possible underlying pathways, such as dietary behaviour.International Journal of Obesity accepted article preview online, 31 July 2013. doi:10.1038/ijo.2013.141.
International journal of obesity (2005) 07/2013; · 5.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: A genome-wide association study of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent SNPs are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (R2 approximately 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for approximately 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.
[show abstract][hide abstract] ABSTRACT: To assess the associations of folate, homocysteine and vitamin B12 levels of children at birth and their methylenetetrahydrofolate reductase (MTHFR) variants with asthma and eczema in childhood.
This study was embedded in a population-based prospective cohort study (n = 2,001). Neonatal cord blood folate, homocysteine and vitamin B12 levels were measured, and MTHFR C677T and A1298C genotyped. Wheezing and physician-diagnosed eczema were annually obtained by questionnaire until 4 years. At 6 years, we collected information on physician-diagnosed asthma ever and self-reported eczema ever, measured fractional exhaled nitric oxide (FeNO), and interrupter resistance (Rint). Data were analysed with generalized estimating equations or logistic regression: continuous outcomes with linear regression models.
Folate, homocysteine and vitamin B12 levels of children at birth were not associated with wheezing or eczema until 4 years, asthma and eczema ever, or FeNO or Rint at 6 years. In children carrying C677T mutations in MTHFR, higher folate levels were associated with an increased risk of eczema (repeated eczema until 4 years: OR 1.40 (95% CI 1.09-1.80) (SD change) P-interaction = 0.003, eczema ever at 6 years: OR 1.41 (0.97-2.03) P-interaction = 0.011). No interactions between MTHFR and child folate and homocysteine levels were observed for wheezing and asthma.
Folate, homocysteine and vitamin B12 levels of children at birth did not affect asthma- and eczema-related outcomes up to the age of 6 years. Further studies are warranted to establish the role of MTHFR variants in these associations.
[show abstract][hide abstract] ABSTRACT: Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate–increasing and heart rate–decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
[show abstract][hide abstract] ABSTRACT: AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.
[show abstract][hide abstract] ABSTRACT: Two pregnancy cohorts were used to investigate the association between single-nucleotide polymorphisms (SNPs) in genes within the insulin-like growth factor (IGF)-axis and antenatal and postnatal growth from birth to adolescence. Longitudinal analyses were conducted in the Raine pregnancy cohort (n = 1162) using repeated measures of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) from 18 to 38 weeks gestation and eight measures of postnatal height and weight (1–17 years). Replications of significant associations up to birth were undertaken in the Generation R Study (n = 2642). Of the SNPs within the IGF-axis genes, 40% (n = 58) were associated with measures of antenatal growth (P ≤ 0.05). The majority of these SNPs were in receptors; IGF-1R (23%; n = 34) and IGF-2R (13%; n = 9). Fifteen SNPs were associated with antenatal growth (either AC or HC or FL) in Raine (P ≤ 0.005): five of which remained significant after adjusting for multiple testing. Four of these replicated in Generation R. Associations were identified between 38% (n = 55) of the IGF-axis SNPs and postnatal height and weight; 21% in IGF-1R (n = 31) and 9% in IGF-2R (n = 13). Twenty-six SNPs were significantly associated with both antenatal and postnatal growth; 17 with discordant effects and nine with concordant effects. Genetic variants in the IGF-axis appear to play a significant role in antenatal and postnatal growth. Further replication and new analytic methods are required in order to better understand this key metabolic pathway integrating biologic knowledge about the interaction between IGF-axis components.
Journal of Developmental Origins of Health and Disease. 04/2013; 4(02).
[show abstract][hide abstract] ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Diuretics can cause changes in calcium levels due to renal effects. Moreover, calcium levels can also vary as a result of changes in intestinal absorption and in the activity of osteoclastic cells. A marker of osteoclastic bone-resorption activity is the level of urinary free deoxypyridinoline (FDP). Deoxypyridinoline (DP) acts as a cross-link between adjacent collagen chains to provide structural rigidity. Our aim was to investigate the association between use of thiazides and loop diuretics and urinary levels FDP. METHODS: In this follow-up study, data were obtained from the Rotterdam Study, a large population-based prospective cohort study. For a subset of 658 participants, urinary levels of FDP were measured at baseline. Linear regression analysis was performed to assess the association between the use of thiazides and loop diuretics and the urinary levels of FDP. RESULTS: In women, current use of loop diuretics for less than 42 days was associated with an increased level of urinary FDP (+3·43 nmol deoxypyridinoline per mmol urinary creatinine; 95% CI 1·85; 5·02) compared with no use. However, use for a period of more than 42 days was not associated with an increased level of FDP, nor was past use of loop diuretics. For thiazide diuretics, no statistically significant associations were found. WHAT IS NEW AND CONCLUSION: In women, short-term use of loop diuretics is associated with an increased level of FDP, reflecting increased bone resorption by osteoclasts. As the difference disappears with longer term use, the clinical significance is unclear and the value of FDP as a biomarker in this setting is not established. The molecular mechanism for the observed differences in bone fracture rates with use of diuretics remains unclear.
Journal of Clinical Pharmacy and Therapeutics 02/2013; · 2.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: What is already known about this subject Parental obesity is a strong risk factor of childhood obesity. High gestational weight gain is associated with childhood body mass index. Previous studies reported inconsistent associations between parental and child anthropometrics. What this study adds Maternal anthropometrics have stronger effects on fetal anthropometrics than paternal anthropometrics. Maternal body mass index has a stronger effect on longitudinally measured childhood body mass index than paternal body mass index. The strongest effect of gestational weight gain on childhood body mass index was seen at the age of 4 years in mothers with normal body mass index. BACKGROUND: There are limited data regarding the associations of both maternal and paternal anthropometrics with longitudinally measured post-natal growth measures in early childhood. OBJECTIVE: To assess the associations of maternal and paternal anthropometrics with growth characteristics and the risk of overweight in pre-school children. STUDY DESIGN: Population-based prospective cohort study from early foetal life onwards in the Netherlands. METHODS: Maternal pre-pregnancy anthropometrics and gestational weight gain, and paternal anthropometrics were related to foetal and post-natal growth measures and the risk of overweight until the age of 4 years. Analyses were based on 5674 mothers, fathers and their children. RESULTS: Both pre-pregnancy maternal and paternal height, weight and body mass index were associated with corresponding foetal and post-natal anthropometric measures. Maternal body mass index had a significantly stronger effect on childhood body mass index than paternal body mass index. As compared to children from parents with normal body mass index, children from two obese parents had an increased risk of overweight at the age of 4 years (odds ratio 6.52 (95% confidence interval 3.44, 12.38). Maternal gestational weight gain was only among mothers with normal body mass index associated with body mass index and the risk of overweight in the children. CONCLUSION: Maternal and paternal anthropometrics affect early growth in pre-school children differently. Gestational weight gain in mothers without overweight and obesity is related to the risk of overweight in early childhood.
[show abstract][hide abstract] ABSTRACT: Background: Maternal depression and anxiety during pregnancy have been associated with offspring-attention deficit problems. Aim: We explored possible intrauterine effects by comparing maternal and paternal symptoms during pregnancy, by investigating cross-cohort consistency, and by investigating whether parental symptoms in early childhood may explain any observed intrauterine effect. Methods: This study was conducted in two cohorts (Generation R, n = 2,280 and ALSPAC, n = 3,442). Pregnant women and their partners completed questionnaires to assess symptoms of depression and anxiety. Child attention problems were measured in Generation R at age 3 with the Child Behavior Checklist, and in ALSPAC at age 4 with the Strengths and Difficulties Questionnaire. Results: In both cohorts, antenatal maternal symptoms of depression (Generation R: OR 1.23, 95% CI 1.05-1.43; ALSPAC: OR 1.33, 95% CI 1.19-1.48) and anxiety (Generation R: OR 1.24, 95% CI 1.06-1.46; ALSPAC: OR 1.32, 95% CI 1.19-1.47) were associated with a higher risk of child attention problems. In ALSPAC, paternal depression was also associated with a higher risk of child attention problems (OR 1.11, 95% CI 1.00-1.24). After adjusting for maternal symptoms after giving birth, antenatal maternal depression and anxiety were no longer associated with child attention problems in Generation R. Moreover, there was little statistical evidence that antenatal maternal and paternal depression and anxiety had a substantially different effect on attention problems of the child. Conclusions: The apparent intrauterine effect of maternal depression and anxiety on offspring-behavioural problems may be partly explained by residual confounding. There was little evidence of a difference between the strength of associations of maternal and paternal symptoms during pregnancy with offspring-attention problems. That maternal symptoms after childbirth were also associated with offspring-behavioural problems may indicate a contribution of genetic influences to the association.
Journal of Child Psychology and Psychiatry 12/2012; · 5.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: Poor gait is an important risk factor for falls and associated with higher morbidity and mortality. It is well established that older age is associated with worse gait, but it remains unclear at what age this association is first seen. Moreover, previous studies focused mainly on normal walking, but gait also encompasses turning and tandem walking. In a large study of community-dwelling middle-aged and elderly persons we investigated the association of age with gait, focusing on normal walking, turning and tandem walking. In 1500 persons aged 50 years and over, we measured gait using an electronic walkway. Participants performed normal walks, turning and a tandem walk. With principal components analysis of 30 variables we summarized gait into five known gait factors: Rhythm, Variability, Phases, Pace and Base of Support; and uncovered two novel gait factors: Tandem and Turning. The strongest associations with age were found for Variability (difference in Z-score -0.29 per 10 years increase (95% confidence interval: -0.34; -0.24)), Phases (-0.31 per 10 years (-0.36; -0.27)) and Tandem (-0.25 per 10 years (-0.30; -0.20)). Additionally, these factors already showed association with the youngest age groups, from 55 to 60 years of age and older. Our study shows that Variability, Phases and Tandem have the strongest association with age and are the earliest to demonstrate a poorer gait pattern with higher age. Future research should further investigate how these gait factors relate with gait-related diseases in their earliest stages.
[show abstract][hide abstract] ABSTRACT: Hippocampal atrophy on MRI and changes in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in patients with Alzheimer's disease. We examined the association between hippocampal volumes, DTI measures of the hippocampus and memory performance in 892 non-demented persons (age≥55years) across different age groups. Hippocampal volume was segmented on 3D volumetric MRI scans. The segmentations were co-registered to mean diffusivity (MD) and fractional anisotropy (FA) maps to yield mean hippocampal MD and FA measurements. Higher MD of the hippocampus was associated with impaired verbal memory performance. In all persons ≥55years, a higher MD of the hippocampus was associated with a worse memory performance. Hippocampal volumes were very weakly positively associated with delayed recall and only in persons >65years. FA of the hippocampus was not associated with memory performance. Follow-up studies will be needed to determine whether higher MD of hippocampus at younger ages could be an earlier marker of incident Alzheimer's disease than hippocampal volume.
[show abstract][hide abstract] ABSTRACT: Introduction
Blood pressure levels during pregnancy are important risk factors for gestational hypertensive disorders. Non-pregnant women from ethnic minority groups are found to have higher blood pressure levels compared to white women. Little is known about variation in blood pressure development during pregnancy across different ethnic groups.
To investigate ethnic differences in blood pressure levels in each trimester of pregnancy and the risk of gestational hypertensive disorders and the degree to which such differences can be explained by education and lifestyle related factors.
The study included 6215 women participating in a population-based prospective cohort study from early pregnancy onwards in Rotterdam, The Netherlands. Ethnicity was assessed at enrolment. Blood pressure was measured in each trimester. Information about gestational hypertensive disorders was available from medical records. Lifestyle factors included smoking, alcohol, caffeine intake, folic acid supplementation, sodium and energy intake, body mass index and maternal stress. Associations and explanatory pathways were investigated using linear and logistic regression analysis.
Dutch pregnant women had higher systolic blood pressure levels as compared to women in other ethnic groups in each trimester of pregnancy. Compared to Dutch women, Turkish and Moroccan women had lower diastolic blood pressure levels in each trimester. These differences remained after adjusting for education and lifestyle factors. Turkish and Moroccan women had a lower risk of gestational hypertension as compared to Dutch women (OR 0.32; 95% CI: 0.18, 0.58 and OR 0.28; 95% CI: 0.14, 0.58) and Cape Verdean women had an elevated risk of preeclampsia (OR 2.22; 95% CI: 1.22, 4.07). Differences could not be explained by education or lifestyle.
Substantial ethnic differences were observed in blood pressure levels in each trimester of pregnancy and risk of gestational hypertensive disorders. A wide range of potential explanatory variables could not explain these differences.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 07/2012; 2(3):195.
[show abstract][hide abstract] ABSTRACT: CONTEXT:
The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated.
To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction.
DESIGN, SETTING, AND PARTICIPANTS:
Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years).
MAIN OUTCOME MEASURES:
Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk.
The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines.
In a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction.
JAMA The Journal of the American Medical Association 06/2012; 307(23):2499-506. · 29.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: To explore the associations between spinal morning stiffness and lumbar disc degeneration (LDD).
Data from a cross-sectional general population-based study (Rotterdam Study-I) were used. Intervertebral disc spaces and osteophytes of people aged ≥55 years were scored on lumbar lateral radiographs (L1-2 through L5-S1 was scored). Logistic regression analysis was used to explore associations between spinal morning stiffness and two definitions of LDD (i.e., 'narrowing' and 'osteophytes'). Spinal morning stiffness combined with low back pain and its association with LDD was also analyzed. Similar analyses were performed for knee and hip pain, morning stiffness in the legs, and radiographic knee and hip osteoarthritis (OA) in order to compare these associations with those of LDD. All analyses were adjusted for age, gender, and body mass index (BMI).
Lumbar lateral radiographs were scored for 2,819 participants. Both definitions of LDD were associated with spinal morning stiffness: adjusted odds ratio (aOR) 1.3; 95% confidence interval (CI): 1.1-1.6 for 'osteophytes' and aOR 1.8; 95% CI: 1.4-2.2 for 'narrowing'. Both the odds ratios increased when spinal morning stiffness was combined with low back pain: aOR 1.5; 95% CI: 1.1-2.0 for 'osteophytes' and aOR 2.5; 95% CI: 1.9-3.4 for 'narrowing'. When morning stiffness in the legs was combined with knee or hip pain, the associations with radiographic knee or hip OA were: aOR 3.0; 95% CI: 2.1-4.1 for knee OA and aOR 3.1; 95% CI: 1.9-5.0 for hip OA.
Reported spinal morning stiffness is associated with LDD. The associations increased when we combined spinal morning stiffness with low back pain. The magnitude of the association for the definition 'narrowing' is similar to the association between morning stiffness in the legs and knee or hip OA.
Osteoarthritis and Cartilage 06/2012; 20(9):982-7. · 4.26 Impact Factor