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Biomedical subjects

Diederick E Grobbee

Publications and source records attributed to Diederick E Grobbee.

At least 127 records · Page 7Linked to original sources
PubMed2004

Long term consequences of the 1944-1945 Dutch famine on the insulin-like growth factor axis.

The insulin-like growth factor axis is highly responsive to nutritional status and may be involved as one of the underlying mechanisms through which caloric restriction could affect cancer risk. High levels of circulating insulin-like growth factor (IGF)-I, or IGF-I relative to IGF binding protein (IGFBP)-3 have been related to various human cancer types. In a group of 87 postmenopausal women, we found that childhood exposure to the 1944-1945 Dutch famine was associated with increased plasma levels of IGF-I and IGFBP-3, whereas IGFBP-1 and -2 levels were weakly decreased. These results are opposite to immediate responses seen under starvation and we hypothesize that this could indicate a permanent overshoot upon improvement of nutritional status after the famine.

Adolescent↗
PubMed2004

Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative trait loci influencing variation in human menopausal age.

Age at natural menopause may be used as parameter for evaluating the rate of ovarian aging. Environmental factors determine only a small part of the large variation in menopausal age. Studies have shown that genetic factors are likely to be involved in variation in menopausal age. To identify quantitative-trait loci for this trait, we performed a genomewide linkage study with age at natural menopause as a continuous quantitative phenotype in Dutch sister pairs, through use of a selective sampling scheme. A total of 165 families were ascertained using extreme selected sampling and were genotyped for 417 markers. Data were analyzed by Haseman-Elston regression and by an adjusted variance-components analysis. Subgroup analyses for early and late menopausal age were conducted by Haseman-Elston regression. In the adjusted variance-components analysis, 12 chromosomes had a LOD score of > or =1.0. Two chromosomal regions showed suggestive linkage: 9q21.3 (LOD score 2.6) and Xp21.3 (LOD score 3.1). Haseman-Elston regression showed rather similar locations of the peaks but yielded lower LOD scores. A permutation test to obtain empirical P values resulted in a significant peak on the X chromosome. To our knowledge, this is the first study to attempt to identify loci responsible for variability in menopausal age and in which several chromosomal regions were identified with suggestive and significant linkage. Although the finding of the region on the X chromosome comes as no surprise, because of its widespread involvement in premature ovarian failure, the definition of which particular gene is involved is of great interest. The region on chromosome 9 deserves further consideration. Both findings require independent confirmation.

Aging↗
PubMed2004

Design and baseline characteristics of a trial on health effects of soy protein with isoflavones in postmenopausal women.

This study is a double-blind, randomized, placebo-controlled trial to assess the effects of high amounts of phytoestrogens on bone mineral density, cardiovascular diseases, cognitive function, performance in activities of daily life and well being. Participants were healthy postmenopausal women, aged 60-75 years. Between March and September 2000, 202 women were recruited, and, after completion of the baseline measurements, randomized to either soy protein, containing 99 mg naturally occurring isoflavones or placebo (milk protein) daily for 1 year. Analysis of the endpoints will be based on the difference between baseline measurements and measurements at the end of the intervention period with group allocation as independent variable.

Absorptiometry, Photon↗
PubMed2004

Antihypertensive drug therapy and the risk of lower extremity amputations in pharmacologically treated type 2 diabetes patients.

PURPOSE: The objective of this study was to determine the association between different antihypertensive drug therapies and lower extremity amputations (LEAs) in type 2 diabetes patients. METHODS: Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and data on hospitalisations for all 450,000 residents of eight Dutch cities. In a nested case-control study among 12,140 type 2 diabetes patients who used antihypertensive drugs, 26 cases with a first LEA and 94 controls without a LEA matched on age, sex and calendar time were identified. Logistic regression was used to estimate the relative risk of LEA and to adjust for potential confounding factors. RESULTS: Among type 2 diabetes patients who used antihypertensive drugs, subjects who used thiazide diuretics, alone or in combination, had a higher risk of LEA compared to subjects who used Angiotensin Converting Enzyme (ACE) inhibitor monotherapy (crude odds ratio (OR): 6.11 [95% confidence interval (CI): 1.32-28.27]). The use of thiazide diuretics was also associated with an increased risk of LEA when compared to the use of any non-thiazide antihypertensive drug (adjusted OR: 7.04 [1.10-45.30]). The increased risk of LEA associated with the use of thiazides compared to the use of non-thiazides depended on the duration of use (adjusted OR(< or = 365 days), 4.82 [0.61-38.34] and adjusted OR(>365 days), 26.16 [1.02-674.02], p-trend = 0.01). CONCLUSIONS: Treatment with thiazide diuretics compared to treatment with other antihypertensive drugs was associated with excess amputations in type 2 diabetes patients. Due to several limitations of this study, our findings do not preclude the use of thiazides in type 2 diabetes mellitus patients as yet.

Aged↗
PubMed2004

Families and the natural history of blood pressure. A 27-year follow-up study.

BACKGROUND: Previous studies on familial aggregation of blood pressure (BP) have reported data on family history of hypertension. Data on actual parental BP levels and the subsequent natural history of BP in their offspring are scarce. METHODS: In a population-based study with 596 children aged 5 to 19 years, cardiovascular risk factors were measured annually from 1975 through 2002. Parental data were obtained at baseline. Repeated BP measurements were studied as a function of tertiles of age-adjusted BP measured in their parents at baseline. RESULTS: Systolic BP during follow-up was higher in offspring whose parents were both in the highest tertile compared with children whose parents were not in the highest tertile (difference 2.7 mm Hg, 95% confidence interval 0.2 to 5.2). Having both parents in the highest tertile of diastolic BP resulted in a substantially higher diastolic BP ranging from 1.9 mm Hg at age 15 years to 8.5 mm Hg at age 45 years. These differences were adjusted for age, sex, body mass index, total serum cholesterol, smoking habits, and alcohol consumption. CONCLUSIONS: The results of this study indicate that actual parental BP is an important predictor of BP development from childhood into young adulthood. This is important when constituting cardiovascular risk profiles for children and young adults.

Adolescent↗
PubMed2004

Meta-analysis on the effect of off-pump coronary bypass surgery.

OBJECTIVE: To assess the effect of conventional coronary artery bypass surgery (CABG) compared to the off-pump procedure (OPCAB). METHODS: Based on randomised trials found in PubMed and Science Citation Index, an overall odds ratio and 95% confidence interval was calculated for the combined endpoint of mortality, stroke and myocardial infarction. RESULTS: The 18 randomised trials included 1584 patients (783 OPCAB, 801 CABG). The odds ratio was 0.73 (95% CI=0.26; 2.04) at 2-week post-surgery, 0.75 (0.39; 1.42) at 1-month post-surgery, 0.55 (0.28; 1.08) at 3-month post-surgery, and 0.66 (0.38; 1.15) at 1-year post-surgery. CONCLUSIONS: The outcome of this meta-analysis shows favourable results for OPCAB for the combined endpoint of mortality, stroke and myocardial infarction at short and long term follow-up. However, none of the risk reductions reach statistical significance at the conventional level. Based on our results OPCAB appears to be equivalent to CABG.

Cardiopulmonary Bypass↗
PubMed2004

alpha-Tocopherol levels in plasma in new-onset, insulin-dependent diabetes mellitus.

BACKGROUND: Diabetic complications have been related to increased oxidative stress. Plasma antioxidant levels may be affected by hyperglycemia-induced oxidative stress as well as by insulin therapy. We evaluated the immediate effect of insulin treatment and improved metabolic control on the important antioxidant alpha-tocopherol plasma (vitamin E) levels in new-onset, insulin-dependent diabetes mellitus. METHODS: The study was performed in 15 consecutive patients, aged 20-67 years, with new-onset diabetes mellitus requiring acute insulin treatment. Plasma alpha-tocopherol levels were measured before the start of intensive insulin treatment and monthly for 6 months thereafter. Simultaneously, we studied plasma malondialdehyde (MDA) as a reflection of lipid peroxidation. In addition, comparisons were made to a nondiabetic reference group. RESULTS: Baseline alpha-tocopherol levels did not differ from those in nondiabetic subjects. alpha-Tocopherol decreased significantly, from 33.5+/-12.1 mumol/l before treatment to 28.11+/-6.85 mumol/l (-16%) after 1 month of insulin therapy (p<0.04) to 26.6+/-7.03 mumol/l (-20%) after 3 months of insulin therapy (p<0.02). This trend did not change after adjusting for variations in cholesterol levels. After 6 months, alpha-tocopherol was no longer decreased compared to baseline levels (29.6+/-7.4 mumol/l). MDA concentrations at baseline were significantly higher in the diabetic patients (3.79+/-2.91 mumol/l) than in the nondiabetic subjects (1.57+/-0.21 mumol/l, p=0.006). MDA concentrations decreased significantly following the start of insulin treatment. CONCLUSIONS: Patients with new-onset, insulin-dependent diabetes mellitus have alpha-tocopherol levels that are similar to those in normal subjects. Insulin treatment and/or improved metabolic control cause a significant decrease in alpha-tocopherol levels during the first months.

Journal Article↗
PubMed2004

Age at natural menopause is not linked with the follicle-stimulating hormone receptor region: a sib-pair study.

OBJECTIVE: Studies have shown that age at natural menopause is heritable. Mutations in the FSH-receptor have been identified in women with premature ovarian failure (POF) and the FSH-receptor gene may, therefore, be considered a candidate gene for (early) menopausal age. This study investigates whether there is linkage between genetic markers in the FSH-receptor region and (early) age at menopause using a sib-pair design. DESIGN: Sib-pair based linkage analysis. SETTING: Sister pairs and their first-degree family members from The Netherlands. PATIENT(S): The inclusion criteria for a family were natural menopause in upper or lower tail of the distribution of menopausal age in at least two sisters. A total of 126 families with at least one sib-pair were included in this study. Six polymorphic markers encompassing the FSH-receptor gene were genotyped. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Single point and multipoint logarithm of the odds (LOD) scores. RESULT(S): None of the markers showed evidence in favor of linkage with overall age at natural menopause or early age at natural menopause. CONCLUSION(S): Possibly, age at natural menopause in the more or less normal range is not part of the spectrum of phenotypes determined by mutations in the FSH-receptor gene. Alternatively, our results might be explained by genetic heterogeneity in the left tail of the distribution of menopausal age. This can limit the chance of finding a genetic locus, especially if this factor has a modest contribution to the phenotype.

Adult↗
PubMed2004

Atherosclerotic disease regression with statins: studies using vascular markers.

Vascular imaging techniques enable identification of atherosclerosis in the sub-clinical phase and allow assessment of interventions to modify disease progression. Angiography has limited utility for tracking the progression of atherosclerosis because of its invasive nature, limited sensitivity for detecting early lesions and relatively low interscan reproducibility. Intravascular ultrasound (IVUS)an electron beam computed tomography (EBCT) are more sensitive and reproducible; however, available data on their ability for tracking disease progression are few. Measurement of carotid intima media thickness (CIMT) by B-mode ultrasound is a well-validated procedure for this application. In comparison with angiography, CIMT demonstrates greater sensitivity for detecting early atherosclerosis and lipid-rich plaques that are vulnerable to rupture. Continued validation and development of imaging techniques, such as magnetic resonance imaging (MRI), will facilitate the assessment of atherosclerosis progression in intervention studies. Stains are effective low-density lipoprotein cholesterol (LDL-C) lowering agents, and imaging studies have demonstrated their ability to slow progression and promote regression of atherosclerosis. The benefits of therapy on atherosclerosis regression appear to extend to soft atherosclerotic plaques that are still developing and treatment effects are independent of baseline LDL-C level. Hence, imaging studies support early intervention with statins in coronary heart disease patients, irrespective of lipid level.

Clinical Trials as Topic↗
PubMed2004

Genetic programming outperformed multivariable logistic regression in diagnosing pulmonary embolism.

OBJECTIVE: Genetic programming is a search method that can be used to solve complex associations between large numbers of variables. It has been used, for example, for myoelectrical signal recognition, but its value for medical prediction as in diagnostic and prognostic settings, has not been documented. STUDY DESIGN AND SETTING: We compared genetic programming and the commonly used logistic regression technique in the development of a prediction model using empirical data from a study on diagnosis of pulmonary embolism. Using part (67%) of the data, we developed and internally validated (using bootstrapping techniques) a diagnostic prediction model by genetic programming and by logistic regression, and compared both on their predictive ability in the remaining data (validation set). RESULTS: In the validation set, the area under the ROC curve of the genetic programming model was significantly larger (0.73; 95%CI: 0.64-0.82) than that of the logistic regression model (0.68; 0.59-0.77). The calibration of both models was similar, indicating a similar amount of overoptimism. CONCLUSION: Although the interpretation of a genetic programming model is less intuitive and this is the first empirical study quantifying its value for medical prediction, genetic programming seems a promising technique to develop prediction rules for diagnostic and prognostic purposes.

Adult↗
PubMed2004

Estrogen, inflammation and cardiovascular risk in women: a critical appraisal.

The widely shared enthusiasm about the cardioprotective potential of estrogenic compounds has come to an abrupt halt since randomized trials failed to show a cardiovascular risk reduction in postmenopausal women. This was unexpected because observational studies had strongly suggested that hormone replacement therapy would reduce the incidence of cardiovascular disease. Inflammatory activity is considered central in atherogenesis and atherosclerosis progression. Thus, parts of the striking discrepancy between observational and randomized data have been attributed to an estrogen-mediated adverse effect on inflammation. Here, we review the current clinical evidence with respect to the inflammation-modulating effects of different estrogenic compounds as one potential explanatory factor for these divergent findings. We conclude that it is still unclear whether estrogen-modulated inflammation is an important biological factor determining clinical outcome or a mere epiphenomenon.

Aged↗
PubMed2004

Birth weight and carotid intima-media thickness: new perspectives from the atherosclerosis risk in young adults (ARYA) study.

PURPOSE: Although intrauterine growth retardation (IUGR) is associated with increased risk of cardiovascular disease (CVD) in adult life, it is unclear whether the relationship is present at younger ages. Furthermore, current debate suggests that postnatal factors might be at least as important as prenatal conditions. The authors investigated whether low birth weight leads to an increased risk of subclinical atherosclerosis in a population-based sample of 750 Dutch men and women, aged 27 to 30 years. METHODS: Information about birth characteristics was available from the original charts of the Municipal Health Service, Utrecht, The Netherlands. Cardiovascular risk factors were evaluated by a questionnaire. The extent of atherosclerosis, assessed by carotid intima-media thickness (CIMT), was measured in both common carotid arteries. RESULTS: Overall, birth weight was not related to common CIMT. However, in the lowest tertile of birth length an inverse association between birth weight and common CIMT was observed. Moreover, low birth weight was significantly associated with increased common CIMT in those who showed exaggerated postnatal growth. CONCLUSIONS: These findings suggest that low birth weight is only associated with increased common CIMT in young adulthood in those who experienced severe IUGR and in those who showed exaggerated postnatal growth.

Adult↗
PubMed2004

Neuropsychology of academic and behavioural limitations in school-age survivors of bacterial meningitis.

Neuropsychological impairments possibly underlying academic and/or behavioural limitations were studied in 149 school-age survivors of bacterial meningitis, 68 with and 81 without academic and/or behavioural limitations. Academic limitations affected mathematics, reading, and writing. Behavioural limitations were inferred from scores in the clinical range on the Child Behaviour Checklist. These children had been selected from a cohort of 674 children (57% males) who had recovered from non-Haemophilus influenzae type B bacterial meningitis and who had a mean age at infection of 2 years 4 months (range 1mo to 9y 5mo). They had neither 'complex onset' meningitis, prior cognitive or behavioural problems, nor severe disease sequelae. They were assessed with standardized assessment methods a mean of 7.8 years (range 4 to 10.4) after meningitis. Children with limitations (32% of the cohort) performed generically poorly on measures of cognitive functioning, speed, and motor steadiness, rather than having impairments in specific neuropsychological domains. The presence of two or more minor neurological signs was more frequent in the group with than in the group without limitations (30% versus 9%); this may explain the relatively poor speed and motor steadiness of the group with limitations.

Achievement↗
PubMed2004

GSTM1 null genotype, red meat consumption and breast cancer risk (The Netherlands).

OBJECTIVE: We studied whether polymorphisms in N-acetyltransferase 1 and 2 and Glutathione S-transferase M1 and T1 genes modify the association between meat consumption and breast cancer. METHODS: A nested case control was conducted in a Dutch prospective cohort. Breast cancer cases (229) and controls (264) were frequency matched on age, town and menopausal status. RESULTS: There is no relation between any type of meat consumption ( i.e., total meat, processed meat, fresh meat, red meat and white meat) and breast cancer risk. Neither presence of NAT1 or NAT2 rapid genotype, or GSTT1 null genotype, alone or in combination with meat consumption affects breast cancer risk. Absence of GSTM1 shows 46% increased breast cancer risk (OR = 1.46 (95% confidence interval, 95% CI = 1.02-2.09)). When stratifying according to combined 'GSTM1 genotype-meat consumption' categories, breast cancer risk is slightly increased with consumption of red meat both in women with genotype GSTM1 presence (OR = 1.49 and 1.75 for intermediate and high versus low consumption) and in GSTM1 null genotype (OR = 1.18 and 1.02). These increases are statistically not significant. In postmenopausal women a suggestion of an effect of red meat consumption is observed: effects are slightly stronger, although still not statistically significant and without a clear dose-response relation: OR = 1.79 (95% CI = 0.92-3.50) and 1.46 (1.46 (95% CI = 0.76-2.82) for intermediate and high compared to low red meat consumption respectively. Reliable evaluation of interaction is not possible due to the small number of cancers. CONCLUSION: GSTM1 null genotype increases breast cancer risk. Red meat consumption slightly increases breast cancer risk, but the relation is not statistically significant and GSTM1, NAT1, NAT2 and GSTT1 polymorphisms do not modify this relation.

Adult↗
PubMed2004

Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin in subclinical atherosclerosis--the rationale and methodology of the METEOR study.

BACKGROUND: Increased carotid intima media thickness (IMT) is associated with established coronary heart disease (CHD) and is a marker of atherosclerosis. Statins are an effective treatment for dyslipidaemia, and have been shown to retard progression or promote carotid IMT regression in patients at high risk of CHD. Rosuvastatin is a highly efficacious statin, and the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) study is designed to assess the impact of rosuvastatin on carotid IMT progression in low risk subjects with signs of subclinical atherosclerosis. METHODS: In this randomised, parallel-group study, asymptomatic subjects at low risk of cardiovascular disease, but with evidence of atherosclerosis (defined as carotid IMT >or=1.2 mm and <3.5 mm), will receive rosuvastatin (40 mg/day) or placebo for 104 weeks. The study will enrol 840 European and US subjects randomised 5:2 between rosuvastatin and placebo. The primary end point will be the change in carotid IMT from baseline to study end, measured using B-mode ultrasonography. Other efficacy end points include changes in the serum lipid profile and C-reactive protein. Safety parameters will also be assessed. CONCLUSION: The METEOR study will evaluate whether long-term rosuvastatin treatment promotes regression, or slows progression, of subclinical atherosclerosis in asymptomatic subjects at low risk of cardiovascular disease.

Arteriosclerosis↗
PubMed2004

A diagnostic decision rule for management of children with meningeal signs.

In a previous study we devised a diagnostic decision rule to improve management of children with meningeal signs, suspected of having bacterial meningitis. The decision rule aimed to guide decisions on (1) whether a lumbar puncture is necessary in children with meningeal signs, and (2) which children need hospitalisation and empirical antibiotic treatment for bacterial meningitis. In this study we assessed the validity of this rule in an external population of four (paediatric) hospitals in The Netherlands. The decision rule included two scoring algorithms using symptoms, signs and quickly available blood and cerebrospinal fluid (CSF) laboratory tests. To evaluate the discriminative value of both algorithms, the absolute numbers of correctly diagnosed patients and the area under the receiver operator characteristic curve were estimated, and compared with the results from the original population (n = 360). In a 18 month period, we included 226 children, median age 2.2 years, who visited the emergency department with meningeal signs. Bacterial meningitis was present in 25 (11%). Using the scoring algorithms patients could be categorised in groups of increasing risk of bacterial meningitis. The discriminative values of the clinical and CSF algorithm in this new population were similar to those in the original population. In the total population of 586 children with meningeal signs, the rule selected 205 children (35%) who did not need a lumbar puncture and 366 children who did not need empirical treatment (62%). In conclusion, this diagnostic rule performed well in a new population of children with meningeal signs. This diagnostic decision rule is a valuable tool for the clinician when deciding to treat these children for bacterial meningitis and thus improving their management.

Adolescent↗
PubMed2004

Dietary phytoestrogens and breast cancer risk.

BACKGROUND: A high intake of phytoestrogens, particularly isoflavones, has been suggested to decrease breast cancer risk. Results from human studies are inconclusive. OBJECTIVE: We investigated the association between phytoestrogen intake and breast cancer risk in a large prospective study in a Dutch population with a habitually low phytoestrogen intake. DESIGN: The study population consisted of 15 555 women aged 49-70 y who constituted a Dutch cohort of the European Prospective Investigation into Cancer and Nutriton (EPIC; 1993-1997). Data concerning habitual dietary intake in the preceding year were obtained by using a validated food-frequency questionnaire. The content of isoflavones and lignans in relevant food items was estimated through a literature search, the use of food-composition tables, and contact with experts. Newly diagnosed breast cancer cases up to 1 January 2001 were identified through linkage with the Comprehensive Cancer Center Middle Netherlands. Hazard ratios for the disease were estimated by Cox proportional hazard analysis for quartiles of isoflavone and lignan intake. Associations were adjusted for known breast cancer risk factors and daily energy intake. RESULTS: A total of 280 women were newly diagnosed with breast cancer during follow-up. The median daily intakes of isoflavones and lignans were 0.4 (interquartile range: 0.3-0.5) and 0.7 (0.5-0.8) mg/d, respectively. Relative to the respective lowest intake quartiles, the hazard ratios for the highest intake quartiles for isoflavones and lignans were 1.0 (95% CI: 0.7, 1.5) and 0.7 (0.5, 1.1), respectively. Tests for trend were nonsignificant. CONCLUSION: In Western populations, a high intake of isoflavones or mammalian lignans is not significantly related to breast cancer risk.

Aged↗