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Biomedical subjects

D E Grobbee

Publications and source records attributed to D E Grobbee.

At least 235 records · Page 13Linked to original sources

Alcohol, blood pressure and hypertension.

In the last 30 years a large number of cross-sectional studies, a smaller number of prospective cohort studies and several intervention studies have addressed the alcohol-blood pressure relationship. Although a number of questions--such as the validity of measurement of alcohol intake, shape of the alcohol-blood pressure relationship, threshold dose for hypertension, and plausible pathophysiological mechanisms--have not yet been answered satisfactorily, it is clear that a causal association exists between chronic intake of > or = 30-60 g alcohol per day and blood pressure elevation in men and women. To call the alcohol-blood pressure relationship causal is justified because chance and, to a large degree, bias and confounding, have been ruled out as plausible explanations in most observational studies. More importantly, the intervention studies support the observational studies and show a remarkable consistency in demonstrating a potentially valuable decrease in blood pressure when heavy drinkers abstain or restrict their alcohol intake. From the different studies a rule of thumb can be derived: above 30 g of alcohol intake per day an increment of 10 g of alcohol per day increases on average systolic blood pressure by 1-2 mmHg and diastolic blood pressure by 1 mmHg.

Adult↗

Apolipoprotein E genotype, atherosclerosis, and cognitive decline: the Rotterdam Study.

The apolipoprotein E4 allele (APOE epsilon 4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOE epsilon 4 and atherosclerosis on cognitive decline are independent. A population-based follow-up study was performed on 838 subjects who were non-demented at baseline. The Mini Mental State Examination (MMSE) score at follow-up was studied as a function of APOE epsilon 4 and atherosclerosis. Mild, non-significant effects on the MMSE score were found for atherosclerosis in the absence of APOE epsilon 4 and for APOE epsilon 4 in the absence of atherosclerosis. APOE epsilon 4 carriers with two or more indicators of atherosclerosis positive, had a significantly lower MMSE score at follow-up (mean difference -0.7 points; 95% confidence interval -1.1 to -0.2) relative to non-APOE epsilon 4 carriers with no evidence of atherosclerosis. Our findings suggest that the consequences of APOE epsilon 4 and atherosclerosis are not independent, and that particularly APOE epsilon 4 carriers with atherosclerosis are at increased risk of cognitive decline.

Aged↗

The Dutch Vascular Factors in Dementia Study: rationale and design.

Dementia is a rapidly increasing health problem in the industrialized countries. With the ageing of the population the number of demented persons increases both in relative and absolute terms. Obviously, there is a need for prevention and intervention strategies. We describe the methods and baseline findings of a large study aimed at identifying potentially modifiable vascular, thrombogenic, and metabolic determinants of dementia. The study population consists of subjects 55 years of age or older. Since the vascular wall of the cerebral vessels is different from that of the coronary or peripheral vessels, we formed three subgroups in which vascular risk factors for dementia are studied. Subjects with stroke were distinguished from subjects with coronary or peripheral artery disease, and from subjects without stroke or coronary or peripheral artery disease. To obtain a large enough number of subjects with stroke, cases and controls from a stroke registry were combined with cases and controls of a population-based study from the same region. For the diagnosis of dementia the DSM-III-R criteria were used. Extensive information on cardiovascular risk factors was collected, including indicators of atherosclerosis. Blood and urine were sampled to study platelet function and thrombogenic and metabolic factors. The study population consists of 7,466 subjects, of whom 300 were recruited from a hospital-based stroke registry. Coronary or peripheral artery disease was present in 956 subjects and stroke in 617. Dementia was present in 434 (5.8%) of all subjects. The prevalence of dementia was 3.0, 24.0, and 4.4% in subjects with a history of coronary or peripheral artery disease, a history of stroke, and subjects without a history of coronary or peripheral artery disease or stroke, respectively. The study will allow us to investigate the role of vascular factors in dementia, irrespective of its cause.

Adult↗

Reproducibility of computerized ECG measurements and coding in a nonhospitalized elderly population.

The standard 12-lead electrocardiogram (ECG) is used in many epidemiologic studies to diagnose and predict cardiovascular disease. In view of this, knowledge about the reproducibility of ECG measurements and coding is essential. Minute-to-minute, day-to-day, and year-to-year variability of ECG measurements, composite scores, and Minnesota Code classification were assessed by use of a computer program, in 101 nonhospitalized elderly men and women. Interval ECG measurements were more reproducible than amplitude measurements. The best reproducibility was found for the overall QTc interval (coefficient of variation 3.1%, 4.0%, and 5.2% for the minute-to-minute, day-to-day, and year-to-year groups, respectively) and the poorest was found for the Cardiac Infarction Injury Score (coefficient of variation 67.1%, 78.5%, and 94.3%, respectively). Minnesota Code discrepancies occurred in 16%, 19%, and 22% of the ECGs in the minute-to-minute, day-to-day, and year-to-year groups, respectively. Reproducibility within specific code categories was much better. Overall, variability tended to increase with time. In the routine setting, electrode positioning had relatively little effect on total variability.

Aged↗

T-loop morphology as a marker of cardiac events in the elderly.

ST-T wave changes of electrocardiographic (ECG) leads have long been recognized as predictors of future cardiac events, but they only imperfectly characterize T-loop morphology. Using vectorcardiographic (VCG) parameters, we investigated the predictive value of T-loop abnormality for fatal and nonfatal cardiac events in a prospective cohort study among 5,815 elderly. Separately, the predictive value of an easily obtainable T-loop parameter, the T axis, was also assessed. Measurements were determined by a computer program, using VCGs reconstructed from the standard 12-lead ECGs. During the 3 to 6 (mean 4) years of follow-up, 166 fatal and 193 nonfatal cardiac events occurred. Subjects with an abnormal T-loop morphology had increased risks for fatal cardiac events (hazard ratio 4.3; 95% CI 3.0-6.4) and nonfatal cardiac events (3.0; 1.9-4.8). Risks associated with an abnormal T axis alone were only slightly lower. Additional adjustment for established cardiovascular risk indicators resulted in lower, but still highly significant risks. Both T-loop and T-axis abnormalities appear to be strong, independent risk indicators of cardiac events in the elderly.

Aged↗

Exercise testing in patients with chest pain to sumatriptan.

OBJECTIVES: In order to assess whether chest pain attributed to sumatriptan is associated with abnormalities on cardiac exercise testing, we performed a case-control study. SUBJECTS: Cases were selected as consumers of sumatriptan who reported sumatriptan associated chest pain. A reference group was selected randomly from consumers of sumatriptan with the same GP as the case, who reported no chest pain after use of sumatriptan. If possible, controls were matched for age (within 5-year groups) and gender. OUTCOMES: In a total of 74 cases and 55 controls symptom-limited exercise tests were performed. Besides a small difference in age, there were no differences in basic characteristics between cases and controls. Three cases had ST-depression on ECG during exercise. However, none of the variables measured during exercise testing differed significantly between cases and controls. CONCLUSIONS: The prevalence of abnormal exercise tests in patients with sumatriptan-induced chest pain is low, and not statistically different from patients without chest pain after intake of sumatriptan. Routine performance of exercise testing in patients with sumatriptan-associated chest pain is not recommended.

Adult↗

Differences in perceived and presented adverse drug reactions in general practice.

BACKGROUND: Postmarketing surveillance (PMS) studies are frequently based on data from general practitioners (GPs). Patients, however, do not always report to their GP suspected adverse drug reactions. SETTING: A postmarketing cohort study on adverse reactions to sumatriptan, performed with assistance of drug dispensing GPs in The Netherlands. METHODS: Questionnaires were sent to all drug-dispensing GPs in The Netherlands, as well as to their patients on sumatriptan. To avoid bias, no specific adverse reactions were mentioned in the questionnaires. RESULTS: Of the GPs, 589 (86%) responded; of the patients, 1202 (70%) responded. The most frequently reported suspected adverse reactions to sumatriptan reported by the GPs were dizziness (1.7%), nausea or vomiting (1.5%), drowsiness or sedation (1.4%), and chest pain (1.3%). The most frequently reported suspected adverse reactions by the patients were paraesthesia (11.7%), dizziness (8.1%), feeling of heaviness (8.0%), and chest pain (7.9%). Neither the GPs nor the patients reported serious adverse reactions. CONCLUSIONS: First, patients experience significantly more suspected adverse reactions than are registered by their GP. In view of this higher frequency of reporting of suspected adverse reactions, postmarketing studies with data from GPs only, may underestimate the cumulative incidence of adverse reactions. Second, we conclude that it is possible to obtain useful additional information about adverse drug reactions from patients by sending them questionnaires via their GP.

Adult↗

The infrarenal aortic diameter in relation to age: only part of the population in older age groups shows an increase.

OBJECTIVES: To resolve whether the infrarenal aortic diameter (IAD) continues to increase throughout life; to ascertain the relationship between IAD and age, sex, body size, and smoking status, and to determine whether these factors influence the IAD over the entire range of aortic diameters or only in a proportion. SETTING: Combined cross-sectional data from two population-based screening programmes for abdominal aortic aneurysms (AAA) in Huntingdon (U.K.) and Rotterdam (The Netherlands). METHODS: The antero-posterior diameter of the infrarenal aorta was measured. The influences of age, gender, body size and smoking status were examined. RESULTS: Data were analysed from 3066 women and 8270 men. In men, mean IAD rose from 20.7 mm to 23.5 mm in the older age groups. However, IADs remained constant below the 75th perentile in men and the 85th percentile in women. Similarly only the top 15-25% of the aortic diameters were larger in smokers compared with non-smokers. CONCLUSIONS: The aortic diameter increased with age in only a minority of the population. Furthermore, known risk factors for AAA contributed to aortic dilatation in only the upper tail of the frequency distribution. Thus only 25% of men and 15% of women may be prone to aortic dilatation.

Age Factors↗

Methodological aspects of physical activity assessment in epidemiological studies.

A range of epidemiological studies conducted over the past decades has produced strong support for the view that lack of physical activity is associated with increased risks of several chronic diseases, such as cardiovascular disease, diabetes mellitus, cancer, etc. Much is still unknown about the type and degree of activity that is required to influence the risk of specific diseases. Furthermore, physical activity can act as a confounder in relationships between other exposure variables (e.g. diet) and disease. Thus, the measurement of physical activity in epidemiological studies is of great importance. The questionnaire is the most frequently used method in epidemiological research. Before using a questionnaire on a large scale, validity and reproducibility should be assessed in a representative population. Some practical and methodological aspects of physical activity validation studies are described, together with the possible implications of the results.

Epidemiologic Methods↗

Dietary assessment in the elderly: validation of a semiquantitative food frequency questionnaire.

OBJECTIVE: The study was conducted to assess the relative validity of a 170-item semiquantitative food frequency questionnaire (SFFQ) adapted for use in the elderly. DESIGN AND SUBJECTS: The study was carried out in a sample of 80 men and women aged 55-75 y participating in a community based prospective cohort study in Rotterdam, The Netherlands. The two-step dietary assessment comprised a simple self-administered questionnaire (20 min) followed by a structured interview with trained dietitians (20 min) based on the completed questionnaire. Multiple food records (FR) collected over a one year period served as reference method. 24 h urine urea was used as indirect marker for protein intake. RESULTS: Compared with FR, the SFFQ generally overestimated nutrient intake as reflected by difference in means and the ratio of SFFQ to FR. Energy adjustment reduced the observed overestimation. Pearson's correlation coefficients varied from close to 0.5 to about 0.9 for crude data, and after adjustment for age, sex, total energy intake, and for within-person variability in daily intake for 0.4-0.8. Cross-classification into quintiles resulted in correct classification into the same or adjacent quintile of 75.8% for crude and 76.8% for energy-adjusted data. Validation of protein intake estimated by SFFQ with protein excretion from 24h urine urea indicated overestimation of protein intake by SFFQ. Spearman correlation coefficient between protein intake estimated from urea excretion and SFFQ was 0.67. CONCLUSIONS: Adaptation of a SFFQ for use in the elderly resulted in a valid and time-efficient dietary assessment instrument. Its ability to adequately rank study subjects according to their dietary intake support its application in epidemiological studies in the elderly.

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Dutch case-control study of anaesthesia-related morbidity and mortality. Rationale and methods.

To date, anaesthesia-related mortality, morbidity and risk factors have almost exclusively been studied qualitatively rather than quantitatively. Therefore, knowledge of the relative risk associated with many anaesthesia-related factors is still lacking. Recently, a quantitative study of the determinants and prevention of morbidity and mortality in anaesthesia was started in the Netherlands. Its objective is to study severe peri-operative morbidity and mortality as a function of anaesthesia-related risk factors. The study is designed as a case-control study within a prospectively defined cohort. The cohort comprises all patients undergoing an anaesthetic procedure, either general, regional or a combination, in one of 61 hospitals between 1 January 1995 and 1 January 1997. A 'case' is a patient who dies within 24 h of undergoing an anaesthetic procedure or who remains comatose 24 h after an anaesthetic procedure. A 'control' patient is a randomly chosen patient who has undergone anaesthesia and is matched for gender and age. The present report discusses the study protocol.

Anesthesia↗

Risk factors for mortality in users of ibopamine.

AIMS: In September 1995, the indication for the oral dopamine agonist ibopamine was restricted in the Netherlands and in several other European countries to patients with NYHA-class II heart failure as a result of an interim analysis of the PRIME-II trial. This trial demonstrated an increased risk of mortality in patients with NYHA-class III/IV heart failure on ibopamine. In September 1995, we initiated an assessment of the effects of ibopamine under everyday circumstances in a cohort of users of ibopamine in all NYHA-classes. METHODS: In a nationwide retrospective cohort study all 2147 community pharmacies and drug dispensing general practitioners received a request to list all patients to whom they had dispensed ibopamine in the preceding years. All responding drug dispensing outlets (DDO) received a questionnaire on cardiovascular risk factors and mortality for the general practitioner of a random sample of these patients. DDO were also requested to send an anonymised printout of the complete medication record. On the end-date of follow-up, February 15th 1996, mortality rates were compared across categories of ibopamine use, adjusted for potential confounders. To assess medication use, drug exposure was compared in a 3 months' period before date of death in the deceased, and before a random date in those patients who were still alive. RESULTS: In patients with NYHA-class III/IV heart failure, multivariate analysis indicated that current use of ibopamine was significantly associated with mortality (RR 1.37;95% CI: 1.15-1.64). In patients with NYHA-class I/II heart failure, however, multivariate analysis showed a 2.03 (95% CI: 1.10-3.72) risk of mortality in current users of ibopamine. Apart from current use of ibopamine, male gender and increased serum creatinine were also independent risk factors for mortality in all NYHA-classes. No statistically significant association was found between mortality and current use of amiodarone or use of amiodarone at baseline. CONCLUSIONS: The increased risk of mortality in patients with NYHA-class III and IV heart failure on ibopamine seems to confirm the main finding of the recently published PRIME-II trial. However, our results indicate that also patients with NYHA-class I/II heart failure may be at an increased risk of mortality when using ibopamine. Additional research on the effects of ibopamine in these patients is warranted and the use of ibopamine in NYHA-class II heart failure patients may have to be reconsidered.

Aged↗

Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population: relation to age and sex steroid levels.

BACKGROUND: Most previous studies concerning the relationship between IGF-I and age used assays measuring total IGF-I. Although free IGF-I is considered of greater biological relevance, little is known about its relationship with sex steroids levels in elderly healthy subjects. MEASUREMENTS: In a cross-sectional study of 218 healthy people (103 men, 115 women) aged 55-80 years we measured serum total and free IGF-I, IGFBP-1 and IGFBP3 levels and sex steroids. Free androgen index and free oestradiol index were used as an indicator for free oestradiol and free testosterone levels, respectively. RESULTS: Free IGF-I levels did not decline with age in the whole study population. Free IGF-I levels even increased in individuals above 70 years of age in comparison to those aged between 55 and 70 years (mean +/- SE 0.106 +/- 0.007 nmol/l vs. 0.086 +/- 0.004 nmol/l, P = 0.009). Total IGF-I and IGFBP-3 decreased with age (r = -0.20, P = 0.005 and r = -0.24, P = 0.001, respectively). Total IGF-I levels were positively related with free oestrogen index in both sexes. Free IGF-I did not relate to free oestrogen or androgen index. In women only, free IGF-I was related positively with DHEAS while IGFBP-1 was inversely correlated with DHEAS. CONCLUSIONS: Free IGF-I levels do not decrease with age and are even higher in individuals above 70 years. There was no relationship between free IGF-I and free androgen or oestrogen index in either gender. We hypothesize that higher free IGF-I levels in older persons may be the consequence of selective survival in the cohort: subjects with high free IGF-I levels may live longer. The absence of a relationship between free IGF-I levels and free androgen and oestrogen indices suggests that there is no direct interaction between the biological activity of circulating IGF-I levels and sex hormone production in a healthy ageing population.

Age Factors↗

The acute effect of dexamethasone on plasma leptin concentrations and the relationships between fasting leptin, the IGF-I/IGFBP system, dehydroepiandrosterone, androstenedione and testosterone in an elderly population.

OBJECTIVE: To investigate the acute effect of dexamethasone administration on serum leptin levels and the relationships between dehydroepiandrosterone (DHEAS), androstenedione, testosterone and the IGF-I/IGFBP system and leptin levels in healthy elderly humans. METHODS: In 209 healthy elderly individuals (95 men, 114 women, aged 55-80 years) measurements were made in the fasting state (0800 h) and after an overnight dexamethasone suppression test (1 mg p.o. at 2300 h. RESULTS: Mean leptin levels increased from 6.2 +/- 0.4 (SE) micrograms/l to 7.3 +/- 0.5 (SE) micrograms/l in men and from 18.9 +/- 1.4 (SE) micrograms/l to 23.9 +/- 1.8 (SE) micrograms/l in women after 1 mg dexamethasone overnight ('post treatment')(P < 0.001 for both sexes). There was a significant relationship between post-treatment leptin and dexamethasone levels (men: P = 0.002; women: P < 0.001). The increase in leptin levels after dexamethasone administration was only partially related to the increase in plasma insulin concentrations. Cortisol levels were not related to leptin. In multivariate analyses the relationship between post-treatment leptin and dexamethasone levels remained after adjustment for post-treatment insulin levels, BMI, waist:hip ratio (WHR) and age (men: P < 0.001; women: P = 0.001). Plasma (free and total) IGF-I and IGFBP-3 levels were not related to leptin levels in men or women. IGFBP-1 levels were inversely related to leptin levels (P = 0.02), but this relationship was lost after adjustment for insulin, and/or BMI. In multivariate analyses the relationship between leptin and DHEAS was inverse in women (P = 0.04) (after adjustment for BMI, WHR, insulin and glucose), while there was no relationship between leptin and DHEAS in men. CONCLUSIONS: Administration of dexamethasone acutely increased leptin levels within 9 h in this elderly population. This increase was only partly related to changes in circulating insulin concentrations, but was independent of BMI and waist:hip ratio. No relation existed between leptin and (free or total) IGF-I and IGFBP-3 in men or women. Dehydroepiandrosterone was inversely related to leptin in women. These findings suggest a contributory regulatory role for corticosteroids in modulating circulating leptin concentrations in elderly healthy individuals of both sexes, which is at least in part independent of insulin, BMI and waist:hip ratio. Dehydroepiandrosterone might play a role in the gender-specific differences in serum leptin levels.

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Lack of associations between serum leptin, a polymorphism in the gene for the beta 3-adrenergic receptor and glucose tolerance in the Dutch population.

BACKGROUND: The associations between leptin levels and the prevalence of a polymorphism in the beta 3-adrenergic receptor were studied in a cross-sectional analysis of 600 participants in a population-based study, which were stratified for glucose tolerance by an oral glucose tolerance test. METHODS: In a random sample of 600 participants in the Rotterdam study, aged 55-75 years at baseline (309 men, 291 women) the relationships were studied between the presence of Trp64 Arg mutation in the beta 3-adrenergic receptor gene and fasting leptin, glucose and insulin (fasting and after an oral glucose load), and other components of the insulin resistance syndrome. RESULTS: Mean age of the study population was 66.9 years (SD 5.7). Fasting serum leptin levels overall in men and women were 6.1 micrograms/l (SE 0.2) and 21.7 micrograms/l (0.9), respectively, (P < 0.001). These differences were independent of age, body mass index and waist to hip ratio. We identified 73/600 persons who were heterozygotes for the Trp64 Arg polymorphism (allelic frequency 6.1%), but failed to find an association between the presence of this polymorphism and leptin or any measured parameter indicative for obesity, impaired glucose tolerance or type 2 diabetes mellitus. CONCLUSION: Heterozygosity for the Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not accompanied by obesity, impaired glucose tolerance and type 2 diabetes mellitus in the general elderly Dutch population, and is also not associated with changes in circulating leptin levels.

Aged↗

Diet and pravastatin in moderate hypercholesterolaemia: a randomized trial in 215 middle-aged men free from cardiovascular disease.

OBJECTIVE: To evaluate the effect of diet and drug intervention separately and combined in the treatment of primary hypercholesterolemia. DESIGN: The study was conducted as a randomized, placebo-controlled factorial trial, double-blinded for drug intervention. SETTING: Subjects were recruited from a population-based cholesterol screening programme. SUBJECTS: 215 middle-aged men with primary hypercholesterolemia, free from cardiovascular disease. INTERVENTIONS: Subjects were randomized to one of four intervention groups: (1) placebo and US National Cholesterol Education Program step 1 diet; (2) placebo and step 2 diet; (3) pravastatin 20 mg day-1 and step 1 diet; or (4) pravastatin 20 mg day-1 and step 2 diet. The intervention period was 6 months. MAIN OUTCOME MEASUREMENTS: Efficacy measurements included: serum total cholesterol, HDL cholesterol, triglycerides, apolipoproteins A1 and B. LDL cholesterol was calculated. For safety, values of ALAT, ASAT and CK were measured. RESULTS: In the group receiving the step 1 diet only, lipid values were stable during the study period. In the placebo group on the step 2 diet, total cholesterol decreased by 6.3% (0.47 mmol L-1 (95% CI: 0.28, 0.67)) during 6 months. In the group receiving both pravastatin and the step 1 diet, there was a mean reduction in serum total cholesterol of 19.4% (1.46 mmol L-1 (95% CI: 1.20, 1.72)). In the group treated with pravastatin and the step 2 diet, the 6 months of data show a reduction of 20.7% (1.55 mmol L-1 (95% CI: 1.30, 1.80)). CONCLUSIONS: If drug therapy with a HMG-CoA reductase inhibitor is considered necessary, a step 2 diet has no additional lipid-lowering effect compared with a step 1 diet in men with primary hypercholesterolaemia. However, favourable 'side-effects' of a lipid-lowering diet, such as weight loss and lowering of blood pressure, may still warrant a low-fat diet in these cases.

Anticholesteremic Agents↗

Genetic association of apolipoprotein E with age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease-associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD, we performed a genetic-association study among 88 AMD cases and 901 controls derived from the population-based Rotterdam Study in the Netherlands. The APOE polymorphism showed a significant association with the risk for AMD; the APOE epsilon4 allele was associated with a decreased risk (odds ratio 0.43 [95% confidence interval 0.21-0. 88]), and the epsilon2 allele was associated with a slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2. 82]). To investigate whether apoE is directly involved in the pathogenesis of AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found that apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that APOE is a susceptibility gene for AMD.

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