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Biomedical subjects

Diederick E Grobbee

Publications and source records attributed to Diederick E Grobbee.

At least 163 records · Page 9Linked to original sources
PubMed2003

Circulating levels of insulin-like growth factor I, its binding proteins -1,-2, -3, C-peptide and risk of postmenopausal breast cancer.

Higher levels of circulating Insulin-like Growth Factor (IGF)-I may be associated with higher risks for premenopausal breast cancer. We investigate the associations between circulating levels of IGF-I, its binding proteins (IGFBPs) -1, -2, -3, C-peptide and postmenopausal breast cancer. This is a prospective study nested in 2 Dutch cohorts. The study population included women who were postmenopausal at baseline. Breast cancer cases were identified through linkage with cancer registries. Controls were matched to cases by cohort, age, date of blood donation and place of residence. In total, 149 breast cancer cases and 333 healthy controls were included. Plasma levels of IGF-I, IGFBP-1, -2, -3 and C-peptide were measured by radioimmunoassays. Estimates of the relative risk for breast cancer associated with the quartiles of the peptides' circulating levels were obtained by conditional logistic regression. Models were adjusted for BMI, age at menarche and age at first full-term delivery. For IGF-I, the adjusted OR (95% CI) of the top vs. bottom quartile was 1.1 (0.6; 2.1); for IGFBP-1 it was 0.7 (0.3; 1.3); for IGFBP-2, 1.1 (0.5; 2.4); for IGFBP-3, 1.6 (0.7; 3.5), for C-peptide, 1.3 (0.7; 2.7) and for IGF-I/IGFBP-3 ratio, 1.0 (0.5; 1.8). Our data do not support an association between postmenopausal circulating levels of IGF-I, IGFBP-1, -2, -3, C-peptide and postmenopausal breast cancer.

Aged↗
PubMed2003

Does the beneficial effect of HRT on endothelial function depend on lipid changes.

OBJECTIVES: To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. METHODS: Hundred-and-five healthy postmenopausal women, aged 50-65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. RESULTS: Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: -0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: -18%; -7%), LDL-cholesterol with 23% (95% CI: -30%; -15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: -26%; -2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. CONCLUSIONS: The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids.

Aged↗
PubMed2003

Plasma and urinary sex hormones are differently related to lipids in healthy postmenopausal women.

OBJECTIVE: Endogenous sex hormones can be measured in plasma and urine. We determined the extent to which these two methods provide different information on hormonal status by relating them to lipid profile in postmenopausal women. METHODS: Thirty healthy postmenopausal women collected one 24-h urine sample and a blood sample was taken. Urinary estrone (UE), plasma estrone (PE) and serum lipids were measured. Sex hormone levels were measured with specific radioimmunoassays. Linear regression analysis was used to determine associations between estrone levels and lipids. Results are presented as beta-coefficients in mmol/l per standard deviation (SD) of endogenous estrone levels, adjusted for body mass index (BMI) and smoking (95% confidence interval). A stratified analysis for obese (BMI> or =27 kg/m(2)) versus lean women was performed. RESULTS: Mean levels of endogenous sex hormones were (SD): PE, 90.1 pmol/l (37.3); and UE, 7757 pmol/24 h (2659). PE showed significant associations with HDL-cholesterol (0.18 mmol/l, 95% CI: 0.06; 0.30), triglycerides (-0.25 mmol/l, 95% CI: -0.49; -0.009) and very-low-density-lipoprotein (VLDL-cholesterol) (-0.11 mmol/l, 95% CI: -0.22; -0.003), but not with total and low-density-lipoprotein (LDL-cholesterol). UE was inversely associated with total (-0.41 mmol/l, 95% CI: -0.85; 0.02) and LDL-cholesterols (-0.42 mmol/l, 95% CI: -0.83; -0.005), but not with HDL-cholesterol, triglycerides and VLDL-cholesterol. All associations appeared to be stronger in lean women. CONCLUSION: Both plasma and UE levels appear to be associated to serum lipids in healthy postmenopausal women. However, this relation appears to be different for estrone levels in plasma and urine. Depending on the research question, either blood samples or urine samples may be preferred.

Body Mass Index↗
PubMed2003

A comparison of on-pump and off-pump coronary bypass surgery in low-risk patients.

BACKGROUND: The performance of coronary bypass surgery without cardiopulmonary bypass ("off pump") may reduce perioperative morbidity and costs, but it is uncertain whether the outcome is similar to that involving the use of cardiopulmonary bypass ("on pump"). METHODS: In a multicenter, randomized trial, we randomly assigned 139 patients with predominantly single- or double-vessel coronary disease to on-pump surgery and 142 to off-pump surgery. Cardiac outcome and cost effectiveness were determined one year after surgery. The uncertainty surrounding the cost-effectiveness ratio (cost differences per quality-adjusted year of life gained) was addressed by bootstrapping. RESULTS: At one year, the rate of freedom from death, stroke, myocardial infarction, and coronary reintervention was 90.6 percent after on-pump surgery and 88.0 percent after off-pump surgery (absolute difference, 2.6 percent; 95 percent confidence interval, - 4.6 to 9.8). Graft patency in a randomized subgroup of patients was 93 percent after on-pump surgery and 91 percent after off-pump surgery (absolute difference, 2.0 percent; 95 percent confidence interval, - 6.5 to 10.4). On-pump surgery was associated with $1,839 in additional direct costs per patient ($14,908 vs. $13,069--a difference of 14.1 percent) and an increase in quality-adjusted years of life of 0.83 as compared with 0.82 (difference, 0.01 year; 95 percent confidence interval, - 0.03 to 0.04). Off-pump surgery was more cost effective than on-pump surgery in 95 percent of bootstrap estimates. CONCLUSIONS: In low-risk patients, there was no difference in cardiac outcome at one year between those who underwent on-pump bypass surgery and those who underwent off-pump surgery. Off-pump surgery was more cost effective.

Cardiopulmonary Bypass↗
PubMed2003

Refill compliance in type 2 diabetes mellitus: a predictor of switching to insulin therapy?

OBJECTIVE: To assess whether switching to insulin therapy in patients with type 2 diabetes mellitus is associated with medication refill compliance of oral hypoglycemic agents. RESEARCH DESIGN AND METHODS: The PHARMO Record Linkage System was used as data source for this study. Patients with newly treated type 2 diabetes mellitus were defined as subjects in whom oral hypoglycemic therapy was initiated between 1991 and 1998. We performed a matched case-control study in this cohort. Cases were patients who switched to insulin therapy. Date of switching in the case was defined as the index date. Controls were subjects still on oral therapy on the index date, matched on duration of diabetes and calendar time. We measured the medication refill compliance in the year starting 18 months before the index date and calculated various compliance indices. RESULTS: In total, 411 cases and 411 matched controls were identified. Cases suffered more often from more severe comorbidity and used a higher number of oral hypoglycemic agents and concomitant non-diabetic drugs. The overall compliance rate did not differ significantly between cases and controls, the adjusted odds ratio (OR) was 1.3 (CI 95% 0.6-2.8). After performing multivariate logistic regression modeling, age at onset of diabetes, gender, comedication, combination therapy, and daily dosage frequency, were independently related to switching. CONCLUSIONS: We were unable to confirm the hypothesis that noncompliance with treatment is more prevalent in patients with secondary failure. Other variables, like comorbidity and disease-related factors seem to play a more important role in switching to insulin therapy.

Administration, Oral↗
PubMed2003

A 2-step strategy to reduce the need for methionine-loading tests to diagnose hyperhomocysteinemia.

An increased plasma homocysteine level may increase the risk of cardiovascular disease. The methionine-loading test is commonly used to detect additional subjects with hyperhomocysteinemia who have normal fasting levels of homocysteine but increased post-methionine-load levels. We developed a 2-step strategy to restrict the methionine-loading test to those subjects with intermediate fasting homocysteine levels to confirm the presence of hyperhomocysteinemia. Hyperhomocysteinemia was defined as a fasting plasma homocysteine level of 16.3 micro mol/L or greater in women and 18.8 micro mol/L or greater in men or an increase in plasma homocysteine level after methionine loading of more than 42.3 micro mol/L for both sexes. From the results in 201 patients, 50 years and younger, with manifest atherosclerosis who underwent a methionine-loading test, we derived cutoff points to define an intermediate group of patients who required a methionine-loading test for hyperhomocysteinemia to be ruled out. These cutoff points were validated in a different population of 275 cardiovascular patients of similar age. The prevalence of hyperhomocysteinemia was 30% in the derivation population and 24% in the validation population. To achieve a sensitivity of 90% in diagnosing hyperhomocysteinemia, we set cutoff points of 11.3 and 9.4 micro mol/L for men and women, respectively. When these cutoff points are applied, it is possible to avoid performing the methionine-loading test in 50% to 75% of subjects tested. With a 2-step strategy to diagnose hyperhomocysteinemia, a sensitivity of 90% for the diagnosis of hyperhomocysteinemia can be achieved, and the need for the methionine-loading test is reduced substantially, with 50% to 75% of subjects no longer needing it.

Adult↗
PubMed2003

How to ADVANCE prevention of cardiovascular complications in type 2 diabetes.

Patients suffering from type 2 diabetes are at increased risk of macrovascular and microvascular disease. This review assesses the available evidence for hypertension and hyperglycemia as risk factors for vascular disease in type 2 diabetes mellitus. Several studies showing a benefit of antihypertensive treatment and glucose-lowering therapy on the prevention of macrovascular and microvascular disease are discussed. However, questions remain concerning the overall balance of benefits and risks of intensive target-driven blood pressure and blood glucose control in type 2 diabetes. More well-powered intervention and prevention studies are therefore needed to provide the necessary reliable evidence to answer these questions. The Action in Diabetes and Vascular disease: PreterAx and DiamicroN modified release Controlled Evaluation (ADVANCE) study is discussed as a trial designed to resemble clinical practice that promises to provide answers concerning the value conferred by blood pressure-lowering therapy and intensive glucose control therapy in type 2 diabetes patients at high risk for cardiovascular disease.

Cardiovascular Diseases↗
PubMed2003

The Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study: design and baseline characteristics.

The Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) trial is a three-arm, randomized, placebo-controlled, double-blind study to determine the effect of tibolone 2.5 mg (Org OD 14) and continuous combined conjugated equine estrogens plus medroxyprogesterone acetate (0.625 mg/2.5 mg respectively) on progression of intima-media thickness of the carotid arteries and bone mineral density of the lumbar vertebrae and proximal femur in postmenopausal women. A total of 866 healthy postmenopausal women were recruited in six U.S. centers and five European centers. Duplicate carotid ultrasound examinations of the common carotid artery, the carotid bifurcation, and the internal carotid artery were performed at baseline. Single measurements of bone mineral density of the lumbar vertebrae and proximal femur were obtained at baseline. After randomization, ultrasound examinations were repeated every 6 months for 36 months following baseline, with a duplicate examination at the end of the study. Bone mineral density was measured every 12 months throughout the trial. The primary outcome is change in mean common carotid intima-media thickness (CIMT), defined as the average of the intima-media thickness measurements performed circumferentially at predefined angles for the near and far wall of 10-mm segments of the right and left distal common carotid arteries. Unique new features of the OPAL study are the specifically developed OPAL ultrasound protocol, yielding highly reproducible CIMT measurements, and the use of two experienced core laboratories for CIMT readings (one in the United States and one in Europe) with one common quality assurance and control program. The OPAL study is a large, placebo-controlled trial evaluating the effects of tibolone, as well as one of the first large randomized studies to determine the effects of continuous combined estrogen-progestin therapy on carotid atherosclerosis in healthy postmenopausal women. The OPAL study results are expected to complement other studies on atherosclerosis progression in healthy postmenopausal women.

Aged↗
PubMed2003

Internal and external validation of predictive models: a simulation study of bias and precision in small samples.

We performed a simulation study to investigate the accuracy of bootstrap estimates of optimism (internal validation) and the precision of performance estimates in independent validation samples (external validation). We combined two data sets containing children presenting with fever without source (n=376+179=555; 120 bacterial infections). Random samples were drawn from this combined data set for the development (n=376) and validation (n=179) of logistic regression models. The models included statistically significant predictors for infection selected from a set of 57 candidate predictors. Model development, including the selection of predictors, and validation were repeated in a bootstrapping procedure. The resulting expected optimism estimate in the receiver operating characteristic (ROC) area was compared with the observed optimism according to independent validation samples. The average apparent ROC area was 0.74, which was expected (based on bootstrapping) to decrease by 0.07 to 0.67, whereas the observed decrease in the validation samples was 0.09 to 0.65. Omitting the selection of predictors from the bootstrap procedure led to a severe underestimation of the optimism (decrease 0.006). The standard error of the observed ROC area in the independent validation samples was large (0.05). We recommend bootstrapping for internal validation because it gives reasonably valid estimates of the expected optimism in predictive performance provided that any selection of predictors is taken into account. For external validation, substantial sample sizes should be used for sufficient power to detect clinically important changes in performance as compared with the internally validated estimate.

Bias↗
PubMed2003

Diagnostic research on routine care data: prospects and problems.

A diagnosis in practice is a sequential process starting with a patient with a particular set of signs and symptoms. To serve practice, diagnostic research should aim to quantify the added value of a test to clinical information that is commonly available before the test will be applied. Routine care databases commonly include all documented patient information, and therefore seem to be suitable to quantify a tests' added value to prior information. It is well known, however, that retrospective use of routine care data in diagnostic research may cause various methodologic problems. But, given the increased attention of electronic patient records including data from routine patient care, we believe it is time to reconsider these problems. We discuss four problems related to routine care databases. First, most databases do not label patients by their symptoms or signs but by their final diagnosis. Second, in routine care the diagnostic workup of a patient is by definition determined by previous diagnostic (test) results. Therefore, routinely documented data are subject to so-called workup bias. Third, in practice, the reference test is always interpreted with knowledge of the preceding test information, such that in scientific studies using routine data the diagnostic value of a test under evaluation is commonly overestimated. Fourth, routinely documented databases are likely to suffer from missing data. Per problem we discuss methods that are presently available and may (partly) overcome each problem. All this could contribute to more frequent and appropriate use of routine care data in diagnostic research. The discussed methods to overcome the above problems may well be similarly useful to prospective diagnostic studies.

Bias↗
PubMed2003

Gestational age and birth weight in relation to aortic stiffness in healthy young adults: two separate mechanisms?

BACKGROUND: Impaired vascular development due to intrauterine growth retardation and postnatal-induced vascular damage by an unfavorable cardiovascular risk profile may both cause stiffer arteries in later decades. METHODS: Of 524 young adults, participating in the Atherosclerosis Risk in Young Adults (ARYA) study, data on birth characteristics were obtained from the original medical records of the Municipal Health Service and the extent of aortic stiffness was assessed using carotid-femoral pulse wave velocity (PWV). RESULTS: The PWV showed an inverse trend with gestational age (linear regression coefficient (beta) = -0.07 m/sec per 1 week; P =.064) whereas it was positively related to birth weight (beta = 0.33 m/sec per 1 kg; P =.020), adjusted for blood pressure (BP), gender, age, and each other. After exclusion of the 26 prematurely born infants, the association with gestational age was attenuated (beta = -0.03 m/sec per 1 week; P =.582), whereas the relation with birth weight hardly changed (beta = 0.30 m/sec per 1 kg; P =.041). In an analysis in which we excluded the 26 subjects with diabetic mothers the birth weight-PWV relation was attenuated (beta = 0.21 m/sec per 1 kg; P =.169). CONCLUSIONS: Our findings suggest that prematurity drives the relation of gestational age and PWV, whereas risk of impaired glucose tolerance drives the relation of birth weight and PWV. We hypothesized that two separate mechanisms might be involved in the development of arterial stiffness in healthy young adults.

Adult↗
PubMed2003

Adolescent blood pressure and blood pressure tracking into young adulthood are related to subclinical atherosclerosis: the Atherosclerosis Risk in Young Adults (ARYA) study.

BACKGROUND: Increased blood pressure (BP) in young adulthood is associated with cardiovascular morbidity and mortality. Longitudinal studies of patients at young ages are, however, limited. Our aim was to study the relationships of adolescent BP and tracking of BP into young adulthood with subclinical atherosclerosis, as assessed by carotid intima-media thickness (CIMT), at the age of 28 years. METHODS: The Atherosclerosis Risk in Young Adults (ARYA) study comprises of a community-based sample of 750 subjects aged 27 to 30 years. In the 352 men and 398 women, at least one BP measurement was recorded at a mean age of 13 years in school health records. Recently, all participants completed a questionnaire on cardiovascular risk factors, had a fasting blood sample drawn, and underwent an ultrasound examination of both common carotid arteries to assess CIMT. RESULTS: Linear regression showed that adolescent systolic BP was associated with thickening of the intima-media (an increase of 7.5 microm in CIMT per standard deviation increase in systolic BP; 95% CI 4.3 to 10.6). Similar relations were found for pulse pressure and mean arterial pressure. When sex, age, and body mass index at adolescence and young adulthood and adult BP were taken into account, the relations attenuated, but for pulse pressure they remained statistically significant. Furthermore, subjects who tracked in the highest systolic BP and pulse pressure levels from adolescence into young adulthood showed the thickest CIMT. CONCLUSION: Our findings strengthen the notion that elevated BP at adolescence and a relative increase in BP from adolescence to adulthood unfavorably affect cardiovascular risk, as indicated by increased CIMT.

Adolescent↗
PubMed2003

Sex hormones and male health: effects on components of the frailty syndrome.

Physicians are seeing an increasing number of older male patients with chronic diseases and conditions. However, the potential relevance of low levels of circulating endogenous androgens in connection with these diseases and conditions is generally poorly understood. Research findings have suggested that androgens play a distinct role in bone metabolism, body composition such as muscle and fat mass and fat distribution, cognitive functioning, mood and well being. The aim of this paper is to summarize the currently available data on the association between endogenous androgens and the intermediate or clinically manifest indicators of chronic conditions in men that might contribute to the phenomenon "frailty". The evidence that reductions in endogenous androgens play a role in age-related health problems is circumstantial. Therefore, large-scale randomized trials are needed to establish whether aging males with low serum androgen levels benefit from androgen supplementation.

Abdomen↗
PubMed2003

Differences between general practitioners and cardiologists in diagnosis and management of heart failure: a survey in every-day practice.

BACKGROUND: Data on diagnosis and management of heart failure in every-day care are scarce. AIMS: To compare general practitioners' and cardiologists' diagnostic work-up and management of patients with (suspected) heart failure. METHODS: In a cross-sectional survey we studied a sample of 103 files of patients coded as heart failure in primary care (31 general practices), and 99 files of out-patients coded as heart failure from 9 hospitals in the Netherlands. We defined patients as heart failure "GP patients", when they were managed by a general practitioner without co-treatment of a cardiologist. RESULTS: Patients managed in general practice were older (mean age 79 years (S.D. 8.5) and more often female than "cardiology patients" (mean age 64 years (S.D. 11.7)). Ischaemic heart disease (31 vs. 57%) was more prevalent in "cardiology patients". Additional investigations such as chest radiography (51% vs. 84%), electrocardiography (39% vs. 100%), and (Doppler-) echocardiography (12% vs. 97%) were performed more often in "cardiology patients". Most patients received diuretics (85% vs.79%). Angiotensin converting enzyme inhibitors (40% vs. 76%), beta-blockers (9% vs. 30%), spironolactone (11% vs. 32%), and angiotensin-II-antagonists (6% vs. 13%) were prescribed much more often to "cardiology patients". CONCLUSION: General practitioners more often treat elderly, female patients with heart failure than cardiologists. General practitioners use less additional investigations and prescribe less potentially beneficial medication, compared to cardiologists. Population characteristics only partly explain these differences, suggesting that the physician's attitude has an important bearing on the uptake of treatment.

Adrenergic beta-Antagonists↗
PubMed2003

Application of a diagnostic decision rule in children with meningeal signs: a cost-minimization study.

OBJECTIVES: Recently, we developed a diagnostic rule for the diagnosis and treatment of children with meningeal signs. This rule may provide the physician with a rationale to decide on the use of diagnostic and treatment procedures in these children and to improve their care. In this study, we estimated cost savings of the rule compared with current practice. METHODS: Routine care data of 360 children visiting the emergency department of the Sophia Children's Hospital with meningeal signs between 1988 and 1998 were used. Costs of diagnostic tests and treatment were estimated by using financial accounts of an academic and a general pediatric hospital. The number of procedures actually performed and the resulting cost estimates (i.e. unit costs x volume) were compared with the estimated figures after application of the decision rule. RESULTS: The population of children with meningeal signs comprised 99 with bacterial meningitis (27%), 36 with another serious bacterial infection (10%), and 225 with a self-limiting disease (63%). Application of the rule would reduce lumbar punctures by 12% and hospitalizations for empirical treatment by 15% with the same diagnostic accuracy as current practice. Cost savings were estimated at Euro292 per patient (relative reduction 10%) and were mainly achieved in the treatment course (Euro259). CONCLUSIONS: A diagnostic decision rule for children with meningeal signs has the potential to improve the appropriate use of medical resources, to be cost-effective, and to ascertain the absence of bacterial meningitis earlier.

Adolescent↗
PubMed2003

Rapid N-acetyltransferase 2 imputed phenotype and smoking may increase risk of colorectal cancer in women (Netherlands).

OBJECTIVE: The relationship between smoking and colorectal cancer risk and whether such effect is modified by variations in the NAT2 genotype is investigated. METHODS: In the prospective DOM (Diagnostisch Onderzoek Mammacarcinoom; 27,722 women) cohort follow-up from 1976 until 1987 revealed 54 deaths due to colon or rectal cancer, and follow-up from 1987 to 01-01-1996 revealed 204 incident colorectal cancer cases. A random sample (n = 857) from the baseline cohort was used as controls. Four NAT2 restriction fragment length polymorphisms (RFLPs) were analysed using DNA extracted from urine samples. Rapid or slow acetylator phenotype status was attributed to individuals. RESULTS: Smoking may increase the risk for colon cancer (RR = 1.36, 95% CI 0.97-1.92) as well as for rectal cancer (RR = 1.31, 95% CI 0.76-2.25), although not statistically significant. Rapid NAT2 acetylation did not increase colorectal cancer risk, but in combination with smoking the risk was statistically significant increased, compared to women who had a slow NAT2 imputed phenotype and never smoked (RR = 1.56, 95% CI 1.03-2.37). For colon cancer, but not for rectal cancer the increased risk was statistically significant (RR = 1.67, 95% CI, 1.05-2.67 versus RR = 1.30 95% CI 0.63-2.68). CONCLUSIONS: Our study points to smoking as a risk factor for colon and rectal cancer and, in addition, especially in women with rapid NAT2 imputed phenotype.

Arylamine N-Acetyltransferase↗