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Biomedical subjects

D E Grobbee

Publications and source records attributed to D E Grobbee.

At least 217 records · Page 12Linked to original sources
PubMed1999

Socioeconomic differences in stroke among Dutch elderly women: the Rotterdam Study.

BACKGROUND AND PURPOSE: We sought to assess the association between socioeconomic status and the risk of stroke among elderly women. Methods--The association between socioeconomic status and stroke emerged in cross-sectional and longitudinal data on 4274 female participants of the Rotterdam Study, a prospective, population-based, follow-up study in the Netherlands among older subjects. RESULTS: A history of stroke was more common among women in lower socioeconomic strata. The same trend was observed for the relationship between the lowest socioeconomic groups and the incidence of stroke. Risk factors for stroke were not related to socioeconomic status in a consistent manner. Smoking, history of cardiovascular diseases, and overweight were more common in lower socioeconomic groups. However, socioeconomic differences in hypertension, antihypertensive drug use, prevalence of atrial fibrillation, and prevalence of left ventricular hypertrophy were not observed. The complex of established risk factors could only partly explain the association between socioeconomic status and stroke. CONCLUSIONS: There is a strong association among elderly women between socioeconomic status and stroke. The association could only partly be explained by known risk factors. Our findings indicate that not only the actual risk profile but also risk factors earlier in life may be of importance.

Aged↗
PubMed1999

Stroke incidence and case fatality in southern Greece: the Arcadia stroke registry.

BACKGROUND AND PURPOSE: For Greece, information on incidence of stroke and distribution of type of stroke has not been reported. We determined the incidence of first-ever stroke in men and women, the incidence of stroke by type, and the associated case fatality. METHODS: A population-based registry was established in the Arcadia province, located in eastern central Peloponessos, in the southern part of Greece. Between November 1, 1993, and October 31, 1995, all subjects with a first-ever stroke were identified. For case ascertainment, information from death certificates, hospital records, public health centers, and general practitioners was used. RESULTS: During a 24-month period, 555 subjects with a first-ever stroke were registered. The incidence rates (per 100 000) by age group (18 to 34, 35 to 44, 45 to 54, 55 to 64, 65 to 74, 75 to 84, >/=85 years) for men were 5, 31, 113, 240, 662, 1275, and 3218, respectively. For women, the rates were 11, 18, 48, 196, 478, 1166, and 2137, respectively. Age- and sex-standardized to the European population, the annual incidence rate for subjects aged 45 to 84 years was 319.4/100 000 (95% CI, 283 to 356). In men, cerebral infarction was diagnosed in 81% of cases, intracerebral hemorrhage in 16%, and subarachnoid hemorrhage in 2%. For women, these figures were 85%, 12%, and 3%, respectively. The 28-day case fatality rate was 26.6% (95% CI, 22.9% to 30.2%), with no differences between men and women. Case-fatality increased with age and was higher for intracerebral hemorrhage than for cerebral infarction. CONCLUSIONS: The incidence of stroke in our population-based study ranks low part compared with other European studies. The distribution of stroke types and case fatality rate appear to be similar to those of other industrialized countries.

Adolescent↗
PubMed1999

Increased thromboxane biosynthesis is associated with poststroke dementia.

BACKGROUND AND PURPOSE: It has been suggested that daily intake of aspirin is associated with a reduction of cognitive decline, both in normal and in demented subjects, but the mechanism is unclear. We have therefore studied the relationship between thromboxane (TX) A(2) biosynthesis, as reflected by the urinary excretion of 11-dehydro-TXB(2), and the presence of dementia in patients after acute stroke. METHODS: Patients from the Rotterdam Stroke Databank were screened for dementia between 3 and 9 months after stroke. Patients had a full neurological examination, neuropsychological screening, and, if indicated, extensive neuropsychological examination. Criteria used for the diagnosis of dementia were from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (Revised). Urine samples were taken at the time of screening. Urinary 11-dehydro-TXB(2) was measured by means of a previously validated radioimmunoassay. RESULTS: Dementia was diagnosed in 71 patients, and urine samples were available for 62. Median value (range) of 11-dehydro-TXB(2) was 399 (89 to 2105) pmol/mmol creatinine for demented patients versus 273 (80 to 1957) for 69 controls with stroke but without dementia (P=0.013). No difference was found between 44 patients with vascular dementia, 404 (89 to 2105) pmol/mmol creatinine, and 18 patients with Alzheimer's disease plus cerebrovascular disease, 399 (96 to 1467) pmol/mmol creatinine (P=0.68). In a stepwise logistic regression analysis, in which possible confounders such as use of antiplatelet medication, cardiovascular risk factors, and type of stroke were taken into account, increased urinary excretion of 11-dehydro-TXB(2) remained independently related to the presence of dementia (OR 1.12, 95% CI 1.03 to 1.22 per 100 pmol/mmol creatinine). The difference in metabolite excretion rates between demented and nondemented patients was most prominent within the subgroup of ischemic stroke patients who received aspirin (P<0.01). CONCLUSIONS: Increased thromboxane biosynthesis in the chronic phase after stroke is associated with the presence of but not the type of poststroke dementia. It is particularly apparent in patients on aspirin, thereby suggesting the involvement of extraplatelet sources of TXA(2) production in this setting.

Aged↗
PubMed1999

Prevalence of variants in candidate genes for type 2 diabetes mellitus in The Netherlands: the Rotterdam study and the Hoorn study.

We have analyzed the association of variants in the genes for amylin, insulin receptor, insulin receptor substrate-1 (IRS-1), and coagulation factor V with type 2 diabetes mellitus. Random samples of subjects with type 2 diabetes and controls were taken from two population-based studies, the Hoorn and Rotterdam studies, to reduce the risk of artifactual associations. No association was found for variants in the genes for amylin, IRS-1, and coagulation factor V, nor was there any evidence for epistatic interactions between these gene variants. A significant difference in the frequency of the Arg972 allele of the IRS-1 gene was observed between control subjects from Hoorn and Rotterdam (9.4% vs. 18.6%; P < 0.05). The insulin receptor Met985 variant was found at frequencies of 4.4% and 1.8%, respectively, in type 2 diabetic (n = 433) and normoglycemic patients (n = 799; P < 0.02). Inclusion of data from two other studies yielded a summarized odds ratio of 1.87 (95% confidence interval, 1.06-3.29; P = 0.03). We conclude that the association between the Met985 variant in the insulin receptor gene and type 2 diabetes, which we previously reported in the Rotterdam study, is supported by thejoint analysis with a second population-based study and other studies. The large regional differences in allele frequency of the Arg972 allele of IRS-1 gene makes genetic association studies of this gene less reliable.

Aged↗
PubMed1999

Luteinizing hormone and different genetic variants, as indicators of frailty in healthy elderly men.

We investigated the possible clinical correlates between the serum LH concentration and characteristics of frailty and determined the presence and concentration of a genetic LH variant in an independently living population of elderly men. After exclusion of subjects with severe mobility problems and signs of dementia, 403 healthy men (aged 73-94 yr) were randomly selected from a population-based sample. Total testosterone (T), sex hormone-binding globulin (SHBG), and leptin were determined by RIA. Non-SHBG-bound T was calculated. LH and the presence of the genetic LH variant were measured using immunofluorometric assays. The characteristics of frailty were leg extensor strength using dynamometry, bone mineral density of total body and proximal femur, and body composition, including lean mass and fat mass, measured by dual energy x-ray absorptiometry. Disability was further assessed by the Modified Health Assessment Questionnaire and by a measure of physical performance. LH significantly increased with age and inversely correlated with T and non-SHBG-bound T. LH was inversely related to muscle strength and lean mass, and both relations were independent of T. LH was positively related to self-reported disability (Modified Health Assessment Questionnaire); 12.5% of the study population was heterozygous for the LH variant allele. T levels and the degree of frailty were not different in the wild-type LH group compared with the heterozygote LH variant group. A significant positive relation between LH and fat mass as well as leptin was only present in the heterozygote LH variant group. In conclusion, serum LH levels increases with age in independently living elderly men and correlates inversely with a variety of indicators of frailty. The observed relation between LH and frailty, independent of T, suggests that LH reflects serum androgen activity in a different way than T, possibly reflecting more closely the combined feedback effect of estrogen and androgen. A difference in biological response between the two LH forms is suggested, as a difference exists in the relation between LH and fat mass, respectively, and leptin in the heterozygote LH variant subjects vs. the wild-type LH subjects.

Aged↗
PubMed1999

Heart failure treatments: issues of safety versus issues of quality of life.

Congestive heart failure is an important cause of morbidity and mortality in western countries. The profound impact that congestive heart failure has on life expectancy and quality of life has been a continuous stimulus for the development of new drugs for the treatment of this condition. Despite favourable effects on (aspects of) quality of life in short term studies, several of these new agents have been shown to reduce survival in mortality trials. However, patients with severe congestive heart failure may experience such incapacitating symptoms that the question should be raised as to whether an improvement in quality of life makes the increased risk of mortality associated with these new agents acceptable. Drugs which improve quality of life at the expense of an increased risk of mortality can be of value in the treatment of patients with severe congestive heart failure. However, this is only the case if the probability of improvement in quality of life and prolongation of life expectancy for those using the drug exceeds the probability of improvement in quality of life and prolongation of life expectancy for those not using the drug. Unfortunately, most clinical trials in which both mortality and quality of life are evaluated fail to provide information on this composite probability. Despite disappointing results of some recent mortality trials on new pharmacological treatments of congestive heart failure, sound and well designed clinical trials on innovative heart failure treatments in which these composite probabilities are also assessed should be carried out.

Heart Failure↗
PubMed1999

Fibrinolytic activity in peripheral atherosclerosis in the elderly.

Increased concentrations of plasminogen activator inhibitor type 1 (PAI-1) and of D-dimer have jointly been found in subjects with cardiovascular disease. To understand this apparent paradox of increased inhibition of fibrinolysis (high PAI-1) combined with increased fibrinolytic activity (high D-dimer), we examined the relation between D-dimer, PAI-1 and the activator of fibrinolysis, tissue type plasminogen activator (t-PA) in subjects with varying severity of peripheral atherosclerosis. In 325 subjects selected from the Rotterdam Study, a cohort of 7983 men and women aged 55 years and over, the ankle to brachial systolic blood pressure ratio, t-PA antigen and activity, PAI-1 antigen and D-dimer were measured. T-PA antigen and t-PA activity were, independent from each other, increased with degree of atherosclerosis; t-PA antigen increased with 3.5 ng/ml (SE 1.7, p = 0.04) and t-PA activity with 0.46 IU/ml (0.20, p = 0.02) per unit decrease in ankle to brachial pressure ratio (i.e. increase in atherosclerosis). PAI-1 antigen was not related to atherosclerosis. More marked atherosclerosis was associated with increased D-dimer, mainly in subgroups with PAI-1 antigen below 50 ng/ml, t-PA antigen below 10 ng/ml, or t-PA activity above 1.5 IU/ml. In contrast to current beliefs, we found that only a fraction of the variation of t-PA antigen was due to the variation in circulating PAI-1 antigen. A slight positive association was observed between t-PA antigen and D-dimer. PAI-1 and t-PA activity were not associated with D-dimer concentration. In conclusion, in subjects with peripheral atherosclerosis PAI-1 antigen is not increased, but low PAI-1 levels (and possibly also low levels of t-PA antigen and high levels of t-PA activity) appear to be required to increase circulating D-dimer. This suggests that increased D-dimer levels in subjects with atherosclerosis do not reflect increased inhibition, but rather reflect increased fibrinolysis.

Aged↗
PubMed1999

Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study.

AIMS: To determine the prevalence of heart failure and symptomatic as well as asymptomatic left ventricular systolic dysfunction in the general population. METHODS AND RESULTS: In 5540 participants of the Rotterdam Study (age 68.9+/-8.7 years, 2251 men) aged 55-95 years, the presence of heart failure was determined by assessment of symptoms and signs (shortness of breath. ankle oedema and pulmonary crepitations) and use of heart failure medication. In 2267 subjects (age 65.7+/-7.4 years, 1028 men) fractional shortening was measured. The overall prevalence of heart failure was 3.9% (95% CI 3.0+/-4.7) and did not differ between men and women. The prevalence increased with age, with the exception of the highest age group in men. Fractional shortening was higher in women and did not decrease appreciably with age. The prevalence of left ventricular systolic dysfunction (fractional shortening <=25%) was approximately 2.5 times higher in men (5.5%, 95% CI 4.1-7.0) than in women (2.2%, 95% CI 1.4-3.2). Sixty percent of persons with left ventricular systolic dysfunction had no symptoms or signs of heart failure at all. CONCLUSIONS: The prevalence of heart failure is appreciable and does not differ between men and women. The majority of persons with left ventricular systolic dysfunction can be regarded as having asymptomatic left ventricular systolic dysfunction.

Age Factors↗
PubMed1999

Redundancy of single diagnostic test evaluation.

Diagnostic research and diagnostic practice frequently do not cohere. Studies commonly evaluate whether a single test discriminates between disease presence and absence, whereas in practice a test is always judged in the context of other information. This study illustrates drawbacks of single-test evaluation and discusses principles of diagnostic research. We used data on 140 patients suspected of pulmonary embolism who had an inconclusive ventilation-perfusion lung scan. We evaluated three tests: partial pressure of oxygen in arterial blood (PaO2), x-ray film of the thorax, and leg ultrasound. On the basis of single-test evaluations, ultrasound was most informative. Given a prior probability of 0.27, it had a much better combination of positive and negative predictive value (0.71 and 0.21, respectively) relative to thorax x-ray (0.33 and 0.11) and PaO2 (0.35 and 0.27). The combination of positive and negative likelihood ratio was also more promising for ultrasound (7.3 and 0.7) than for thorax x-ray (1.3 and 0.3) and PaO2 (1.3 and 0.9). As the tests are always performed after the history and physical, we judged their added value using multivariable logistic modeling with receiver operating characteristic (ROC) analyses. The ROC areas of the model, including history and physical, with additional PaO2, thorax x-ray, or ultrasound, were 0.75, 0.77, 0.81, and 0.81, respectively, which indicated similar added value of thorax x-ray and ultrasound. Application of the models to patient subgroups also yielded added predictive value for thorax x-ray film. Thus, the results of single-test evaluations may be very misleading. As no diagnosis is based on one test, single-test evaluations have limited value in diagnostic research and only have relevance in the context of screening and the initial phase of test development. Diagnostic research should always apply an approach of constructing, extending, and validating diagnostic models in agreement with routine clinical work-up using logistic regression analyses.

Analysis of Variance↗
PubMed1999

Serum caeruloplasmin as a coronary risk factor in the elderly: the Rotterdam Study.

Serum Cu and caeruloplasmin levels have been suggested to be independent risk factors for CHD operating through oxidative modification of LDL. However, given its function as an acute-phase protein, the question has been raised whether an elevated caeruloplasmin level is not merely an indicator of inflammation. In the current study, we investigated whether serum caeruloplasmin was associated with subsequent myocardial infarction, taking into account indices of inflammation. The study population consisted of 210 cases of first myocardial infarction and controls, frequency-matched on age (5-year categories) and sex, selected from the population-based cohort of the Rotterdam Study. Serum caeruloplasmin levels were significantly elevated in cases of myocardial infarction compared with controls (510 (SD 110) v. 470 (SD 100) mg/l; P = 0.007). Risk of myocardial infarction for the highest compared with the lowest quartile of caeruloplasmin was 2.46 (95% CI 1.04, 6.00; Ptrend = 0.043) after adjustment for age, sex, BMI, pack-years smoked, serum cholesterol, systolic blood pressure, and income. The relative risk was most evident in current smokers. Adjustment for C-reactive protein and leucocyte count reduced the excess risk by 33%. This suggests that a substantial part of the observed association between serum caeruloplasmin and CHD may be attributed to inflammation processes rather than to the pro-oxidant activity of caeruloplasmin.

Aged↗
PubMed1998

T axis as an indicator of risk of cardiac events in elderly people.

BACKGROUND: The T axis was postulated to be a general marker of repolarisation abnormality, indicative of subclinical myocardial damage. The aim of this investigation was to assess the prognostic importance of the T axis for fatal and non-fatal cardiac events, in a prospective cohort study of men and women aged 55 years and older. METHODS: 2352 men and 3429 women from the population-based Rotterdam Study took part in the study. Electrocardiograms were done, and T axes were categorised as normal, borderline, or abnormal. Data were analysed with Cox's proportional-hazards models; adjustment for age and sex was done where appropriate. FINDINGS: During 3-6 (mean 4) years of follow-up of the 5781 participants, 165 (2.9%) fatal and 192 (3.3%) non-fatal cardiac events occurred. Participants with an abnormal T axis (n=609) had an increased risk of cardiac death (hazard ratio 3.9 [95% CI 2.8-5.6]), sudden cardiac death (4.4 [2.6-7.4]), non-fatal cardiac events (2.7 [1.9-3.9]), and combined fatal or non-fatal cardiac events (3.2 [2.5-4.1]); p<0.001 for each. Additional adjustment for established cardiovascular risk factors resulted in lower, but still significant risk for all endpoints. The risk associated with an abnormal T axis was higher than those for any other cardiovascular risk factor. Additional subgroup analyses indicated that the risk of cardiac death was not substantially modified by age, sex, or history of myocardial infarction. INTERPRETATION: The T axis is a strong and independent risk indicator of fatal and non-fatal cardiac events in the elderly.

Aged↗
PubMed1998

[Lessons from a heart valve prosthesis controversy].

Two lessons are to be learnt from the Björk-Shiley heart valve prosthesis tragedy. In the first place pharmacoepidemiologic studies are seriously hampered by recent privacy legislation. Individual patients carrying such a prosthesis cannot be traced and advised as to their health risks any more, because their legal autonomy has to be respected. This is clearly not to their advantage. In the second place the atmosphere of marketing and litigation and the increasing dependency of researchers on money from sources with conflicting interests is not conducive to a well-informed and balanced judgement of the epidemiological evidence of safety and efficacy of medical treatments.

Conflict of Interest↗
PubMed1998

Breast-cancer incidence in relation to height, weight and body-fat distribution in the Dutch "DOM" cohort.

In a cohort of 11,663 participants in a breast-cancer screening program, height, weight, waist circumference and hip circumference were measured, and information about menstrual and reproductive history was obtained by questionnaire. After exclusion of 83 women with unclear menopausal status, the subjects were divided into 3 sub-cohorts: 5,891 women who were pre-menopausal at the time of data collection, 3,521 women who had entered the study after natural menopause, and 2068 women who had been hysterectomized and/or ovariectomized. After a median follow-up of 10.6 years, 147, 76 and 52 incident cases of breast cancer were detected in the 3 respective sub-cohorts. No statistically significant association was found in any of the sub-cohorts between breast-cancer risk and height, weight, body-mass index (BMI) or hip circumference. In the sub-cohort of women with natural menopause, however, risk of breast cancer was positively and significantly associated with the ratio of waist-to-hip circumferences (WHR) (RR = 2.63 for upper vs. lower quartile), and this association did not change after adjustment for variations in disease risk related to body height and weight. Although similar to observations in other cohort studies showing positive associations between obesity and breast-cancer risk in post-menopausal women, our results are different, in that WHR and not BMI appears to be the more specific indicator of breast-cancer risk.

Adipose Tissue↗
PubMed1998

[Association between the intima-media thickness of the common carotid and subsequent cardiovascular events in subjects, 55 years and older, in the Rotterdam study (ERGO)].

OBJECTIVE: To determine whether common carotid artery intima-media thickness (IMT) is related to future cardiovascular disease. DESIGN: Nested case control study. SETTING: The suburb of Ommoord in Rotterdam, the Netherlands. METHOD: As part of the Rotterdam study among 7983 subjects aged 55 years and over, ultrasound images of the common carotid artery were stored on videotape of 5965 subjects at baseline (1990-1993). Analysis (logistic regression) was based on 190 cases of cardiovascular disease (myocardial infarction and stroke), registered up to December 31, 1994. IMT was measured from videotape for all cases and a control sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. RESULTS: The age and sex adjusted cardiovascular disease risk increased by 45% (95% confidence interval (95% CI): 25-69) per standard deviation increase (0.163 mm) in IMT. Stroke risk increased by 45% (95% CI: 25-69) per standard deviation increase and the risk of myocardial infarction increased by 43% (95% CI: 16-78). Additional adjustment for several cardiovascular risk factors attenuated the association. CONCLUSION: Increased common carotid intima-media thickness was associated with subsequent cardiovascular events. These results support the use of carotid intima-media thickness measurements as a surrogate endpoint in observation and intervention studies. The value of IMT measurements for individual patients and cardiovascular screening merits further study.

Aged↗
PubMed1998

QTc dispersion predicts cardiac mortality in the elderly: the Rotterdam Study.

BACKGROUND: Increased QTc dispersion has been associated with an increased risk for ventricular arrhythmias and cardiac death in selected patient populations. We examined the association between computerized QTc-dispersion measurements and mortality in a prospective analysis of the population-based Rotterdam Study among men and women aged > or = 55 years. METHODS AND RESULTS: QTc dispersion was computed with the use of the Modular ECG Analysis System as the difference between the maximum and minimum QTc intervals in 12 and 8 leads (ie, the 6 precordial leads, the shortest extremity lead, and the median of the 5 other extremity leads). After exclusion of those without a digitally stored ECG, the population consisted of 2358 men and 3454 women. During the 3 to 6.5 years (mean, 4 years) of follow-up, 568 subjects (9.8%) died. The degree of QTc dispersion was categorized into tertiles. Data were analyzed using the Cox proportional hazards model, with adjustment for age. For QTc dispersion in 8 leads, those in the highest tertile relative to the lowest tertile had a twofold risk for cardiac death (hazard ratio, 2.5; 95% confidence interval [CI], 1.6 to 4.0) and sudden cardiac death (hazard ratio, 1.9; 95% CI, 1.0 to 3.7) and a 40% increased risk for total mortality (hazard ratio, 1.4; 95% CI, 1.2 to 1.8). Additional adjustment for potential confounders, including history of myocardial infarction, hypertension, and overall QTc, did not materially change the risk estimates. Hazard ratios for QTc dispersion in 12 leads were comparable to those found for QTc dispersion in 8 leads. CONCLUSIONS: QTc dispersion is an important predictor of cardiac mortality in older men and women.

Age Factors↗