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Biomedical subjects

D E Grobbee

Publications and source records attributed to D E Grobbee.

At least 109 records · Page 6Linked to original sources

Effects of second and third generation oral contraceptives and their respective progestagens on the coagulation system in the absence or presence of the factor V Leiden mutation.

Compared to second generation, the use of third generation oral contraceptives has been associated with an increased risk of venous thrombosis especially in women with the factor V Leiden mutation. To find an explanation for these risk differences we investigated the effects of desogestrel- and levonorgestrel-containing oral contraceptives as well as their progestagens separately on the coagulation system in the absence or presence of the factor V Leiden mutation. In a single center, double blind trial, 51 women without and 35 women with the factor V Leiden mutation were randomized to either a second generation (30 microg ethinylestradiol/150 microg levonorgestrel) or a third generation (30 microg ethinylestradiol/150 microg desogestrel) oral contraceptive. After two cycles of use and a wash-out period of 2 menstrual cycles, the participants received the corresponding progestagen-only preparation containing 150 microg levonorgestrel or 150 microg desogestrel. In plasmas of the participating women fragment 1+2, factor V, VII, VIII, IX, X and XI were determined. Both combined oral contraceptives induced a decrease in factor V, whereas the levels of all other coagulant parameters increased. However, in women without the factor V Leiden mutation the effects of desogestrel-containing preparations were significantly different compared to levonorgestrel-containing oral contraceptives for factor V (-8.0; 95% CI -13.4 to -2.6), factor VII (26.8; 95% CI 15.5 to 38.0) and factor IX (-9.6; 95% CI -16.2 to -3.2). When these women used progestagen-only pills, a differential effect between desogestrel and levonorgestrel was only found for factor IX (-6.5; 95% CI -11.4 to -1.5). In carriers of the factor V Leiden mutation desogestrel-containing oral contraceptives induced more pronounced changes in factor V (-14.2; 95% CI -22.4 to -6.0) and factor VII (36.1; 95% CI 19.7 to 52.6) compared to levonorgestrel-containing oral contraceptives. Comparing desogestrel- and levonorgestrel-only, only for factor V a differential effect was found in these women (-9.5; 95% CI -18.3 to -0.6). It appears that desogestrel-containing oral contraceptives have a more pronounced effect on the coagulation system than levonorgestrel-containing oral contraceptives which may be explained by a less effective compensation of the thrombotic effect of ethinylestradiol by desogestrel.

Activated Protein C Resistance↗

The metabolic syndrome in black hypertensive women--waist circumference more strongly related than body mass index.

OBJECTIVE: To examine the association between measures of obesity and features of the metabolic syndrome in treated black female hypertensive subjects. DESIGN: Cross-sectional study. SETTING: An urban primary health care centre in Mamelodi, Pretoria. SUBJECTS: Women with hypertension and without known diabetes mellitus or secondary causes of hypertension. In total 124 women participated, with a mean age of 56.9 years (standard deviation (SD) 11.0) and mean body mass index (BMI) of 34.1 kg/m2 (SD 8.1). MAIN OUTCOME MEASURES: Blood pressure, glucose, insulin and lipid levels. RESULTS: Waist circumference and waist-hip ratio were more strongly associated with insulin, uric acid, glucose and triglycerides than was BMI. Statistically significant associations were found between waist circumference and low high-density lipoprotein HDL cholesterol (standardised regression coefficient -0.006, standard error of the mean (SEM) 0.002), log triglycerides (0.007, SEM 0.003), uric acid (0.002, SEM 0.001) and log insulin (0.012, SEM 0.003). BMI was only significantly associated with uric acid (0.002, SEM 0.002) and log insulin (0.009, SEM 0.004). CONCLUSION: In a group of black hypertensive women measures of central obesity were more strongly associated with components of the metabolic syndrome than BMI.

Black People↗

Factors associated with switching from oral hypoglycaemic agents to insulin therapy.

BACKGROUND: The aim of our study was to determine which factors are associated with switching from oral hypoglycaemic agents to insulin therapy in patients with type 2 diabetes mellitus in general practice. METHODS: Longitudinal, observational study in a Dutch general healthcare centre. All pharmacologically treated patients with type 2 diabetes mellitus were included (n = 152). Comorbidity, laboratory results and medication use were obtained from the general practitioners' files. RESULTS: A total of 31 (20.4%) patients switched from oral hypoglycaemic agents to insulin therapy; they were significantly younger at the onset of diabetes, 50.5 versus 57.7 years. Fasting blood glucose levels and HbA(1c) values were significantly higher after the switch compared with patients on oral treatment, 10.0 mmol/l versus 8.4 mmol/l and 8.8% versus 7.9%, respectively. Concerning comorbidity, they suffered more frequently from acute myocardial infarction, lipid disorders, depression, retinopathy and atrial fibrillation. Cardiovascular disease in general was more often present in patients who switched over to insulin, 77.4% versus 52.9% (OR 3.1; CI 1.2-7.6). CONCLUSIONS: Patients who switch over to insulin therapy are younger at diagnosis, suffer from more health problems besides diabetes, especially cardiovascular disease, and have worse metabolic control, compared with users of oral hypoglycaemic agents.

Administration, Oral↗

Association between joint bleeds and Pettersson scores in severe haemophilia.

PURPOSE: To assess and quantify the association of haemophilic arthropathy, measured by the radiological Pettersson score, with the number of joint bleeds suffered by the patient. MATERIAL AND METHODS: In order to quantify the effect of the cumulative number of joint bleeds on the Pettersson score, a study was performed using 295 Pettersson scores obtained in 117 patients with severe haemophilia. The patients were born between 1965 and 1994, and had no history of inhibitors. The number of joint bleeds was determined annually from the entry in the clinic and onwards. The localization of bleeds was not assessed. The patients entered the clinic at a median age of 3.6 years, and received intermediate dose prophylaxis, starting at a median age of 5.3 years. Evaluation of 1643 treatment years showed a mean of 6.8 joint bleeds/year. Pettersson scores were obtained at a mean age of 15.9 years (range 1.7-32.9) and had a median value of 4 points (range 0-50). RESULTS AND CONCLUSION: The Pettersson scores began to rise after the age of 5 years and increased with one point for every 13 joint bleeds (95% confidence interval 11-15). No evidence was found of 'autonomous' progression of Pettersson scores, independent of bleeds.

Adolescent↗

[Short preoperative health assessment proposed by the Health Council not useful in clinical practice].

OBJECTIVE: To evaluate the value of the short questionnaire drawn up by the Dutch Health Council for the classification of patients to an ASA class (a 5-point scale according to the American Society of Anesthesiologists, on which the patient's preoperative physical condition can be scored) and to propose an anaesthesia care plan for surgery patients aged between 16 to 40 years old. DESIGN: Observational. METHODS: From June 1999 through to May 2000, all 2090 preoperative patients aged 16 to 40 years at the academic hospital of Utrecht, the Netherlands, were asked to complete the Dutch Health Council's short questionnaire. In addition, the usual extensive preoperative health assessment was carried out on these patients. Of the 379 (18%) who were found by the short questionnaire to be 'healthy', 100 were selected. A panel of 10 anaesthesiologists was asked to preoperatively evaluate these 100 patients twice: once using the short questionnaire and once using the usual extensive health evaluation. The primary outcome was the percentage of patients who could be classified to an ASA class and for whom an anaesthesia care plan could be drawn up. The secondary outcome was the information judged by the anaesthesiologists to be either 'redundant' or 'missing' when drawing up an anaesthesia care plan. RESULTS: Using the short questionnaire, 63% of the patients could not be assigned to an ASA class, compared to 22% with the extensive health evaluation (p < 0.0001). On the basis of the information obtained with the short questionnaire, it was not possible to draw up an anaesthesia care plan for any of the patients, while the extensive health evaluation enabled an anaesthesia care plan to be drawn up for 65% of the patients (95% CI: 62-68%). Using the missing information deemed 'necessary', recommendations were made for the minimum scope of a preoperative health assessment for use in patients aged 16 to 40 years old. CONCLUSION: The short questionnaire as proposed by the Dutch Health Council was not found to be useful in practice.

Adolescent↗

[CBO guideline 'High blood pressure' (revision)].

The revised CBO guideline 'High blood pressure' details the present scientific knowledge about the detection, diagnosis and treatment of elevated blood pressure as well as the implementation of this knowledge in practice. For both systolic and diastolic increased blood pressure the risk of cardiovascular disease and mortality gradually increases. The blood pressure is considered to be elevated if the systolic pressure is > or = 140 mmHg and/or the diastolic pressure is > 90 mmHg. For individuals aged 60 years and over, without diabetes, familiar hypercholesterolaemia or overt cardiovascular disease, 160 mmHg is the cut-off value for elevated systolic pressure. Depending on age or blood pressure level, the diagnosis 'elevated blood pressure' is established after 3 or 5 measurements over a period of some weeks (3 measurements) to 6 months (5 measurements). Where elevated blood pressure is diagnosed, lifestyle recommendations should be considered first and only if these provide insufficient results should medicinal treatments be adopted. The indication area for treatment is laid down in the case of elevated blood pressure and an absolute cardiovascular risk of 20% per 10 years. When the absolute cardiovascular risk is between 10% and 20% per year, treatment may be considered. For treatment the target value is the same as the criterion for elevated blood pressure.

Antihypertensive Agents↗

Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study.

BACKGROUND: The use of cardiopulmonary bypass during coronary artery bypass surgery (CABG) has been associated with substantial morbidity. The recent introduction of cardiac stabilizers facilitates CABG without cardiopulmonary bypass (off-pump CABG), but it is unknown whether cardiac outcome after off-pump surgery is similar to that for the on-pump procedure. METHODS AND RESULTS: In a multicenter trial, 281 patients (mean age 61 years, SD 9 years) were randomly assigned to off-pump or on-pump CABG. In-hospital results and cardiac outcome and quality of life after 1 month are presented. Cardiac outcome was defined as survival free of stroke, myocardial infarction, and coronary reintervention. The mean numbers of distal anastomoses per patient were 2.4 (SD 1.0) and 2.6 (SD 1.1) in the off-pump and on-pump groups, respectively. Completeness of revascularization was similar in both groups. Blood products were needed during 3% of the off-pump procedures and 13% of the on-pump procedures (P<0.01). Release of creatine kinase muscle-brain isoenzyme was 41% less in the off-pump group (P<0.01). Otherwise, no differences in complications were found postoperatively. Off-pump patients were discharged 1 day earlier. At 1 month, operative mortality was zero in both groups, and quality of life had improved similarly. In both groups, 4% of the patients had recurrent angina. The proportions of patients surviving free of cardiovascular events were 93.0% in the off-pump group and 94.2% in the on-pump group (P=0.66). CONCLUSIONS: In selected patients, off-pump CABG is safe and yields a short-term cardiac outcome comparable to that of on-pump CABG.

Cardiopulmonary Bypass↗

Effect of hormone replacement therapy on lipids in perimenopausal and early postmenopausal women.

OBJECTIVE: To determine the effects of oral sequential hormone replacement therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women. METHODS: We performed a single-center, randomized, placebo-controlled trial. The trial was double blind with respect to 17beta-estradiol/desogestrel (17beta-E-D) and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A total of 125 healthy perimenopausal and early postmenopausal women, aged 43-58 years, were recruited from the general population in Zoetermeer, the Netherlands. The intervention consisted of 6 months treatment with 1.5 mg 17beta-estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight fasting blood samples were obtained in which lipids were determined. We used linear regression analysis to calculate differences in mean change from baseline in lipids in the active treatment groups compared to placebo. RESULTS: In both treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)-cholesterol (17beta-E-D: -7.8% and CEE-N: -8.4%) and lipoprotein(a) (17beta-E-D: -11.7% and CEE-N: -28.3%) were found compared to placebo. Apolipoprotein A1 (17beta-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17beta-E-D: 6.4% and CEE-N: 8.0%) significantly increased compared to placebo. No significant changes were found in the other lipids. Mean changes from baseline in total cholesterol, LDL-cholesterol and apolipoprotein B were significantly more pronounced in postmenopausal women compared to perimenopausal women, adjustment for age-differences did not change the results. CONCLUSION: Treatment of perimenopausal and early postmenopausal women with 17beta-E-D or CEE-N changes their lipid-profile in a potentially anti-atherogenic direction. Changes appear to be more pronounced in postmenopausal women compared to perimenopausal women.

Adult↗

Third generation oral contraceptives and risk of venous thrombosis: meta-analysis.

OBJECTIVE: To evaluate quantitatively articles that compared effects of second and third generation oral contraceptives on risk of venous thrombosis. DESIGN: Meta-analysis. STUDIES: Cohort and case-control studies assessing risk of venous thromboembolism among women using oral contraceptives before October 1995. MAIN OUTCOME MEASURES: Pooled adjusted odds ratios calculated by a general variance based random effects method. When possible, two by two tables were extracted and combined by the Mantel-Haenszel method. RESULTS: The overall adjusted odds ratio for third versus second generation oral contraceptives was 1.7 (95% confidence interval 1.4 to 2.0; seven studies). Similar risks were found when oral contraceptives containing desogestrel or gestodene were compared with those containing levonorgestrel. Among first time users, the odds ratio for third versus second generation preparations was 3.1 (2.0 to 4.6; four studies). The odds ratio was 2.5 (1.6 to 4.1; five studies) for short term users compared with 2.0 (1.4 to 2.7; five studies) for longer term users. The odds ratio was 1.3 (1.0 to 1.7) in studies funded by the pharmaceutical industry and 2.3 (1.7 to 3.2) in other studies. Differences in age and certainty of diagnosis of venous thrombosis did not affect the results. CONCLUSIONS: This meta-analysis supports the view that third generation oral contraceptives are associated with an increased risk of venous thrombosis compared with second generation oral contraceptives. The increase cannot be explained by several potential biases.

Adult↗

Dietary antioxidants and peripheral arterial disease : the Rotterdam Study.

This study examined cross-sectionally the association of dietary beta-carotene, vitamin C, and vitamin E with peripheral arterial disease in Rotterdam, the Netherlands (1990--1993). The 4,367 subjects from the Rotterdam Study were aged 55--94 years and had no previous cardiovascular disease at baseline. Diet was assessed with a food frequency questionnaire. Peripheral arterial disease was defined as an ankle-arm systolic blood pressure index (AAI) of < or = 0.9 and was present in 204 men and 370 women. In multivariate-adjusted logistic regression analyses, vitamin C intake was significantly inversely associated with peripheral arterial disease in women (highest vs. lowest quartile: relative risk = 0.64, 95% confidence interval (CI): 0.48, 0.89; p(trend) = 0.006), and a 100-mg increase in intake was associated with a 0.013 AAI increase (95% CI: 0.001, 0.025). In men, vitamin E intake was inversely associated with peripheral arterial disease (relative risk = 0.67, 95% CI: 0.44, 1.03; p(trend) = 0.067); a 10-mg increase in intake was associated with a 0.015 AAI increase (95% CI: 0.001, 0.031). Whether these differences in antioxidant intake and the risk of a low AAI and of peripheral arterial disease between sexes are attributable to a different food pattern for men compared with women remains to be elucidated.

Aged↗

[Implanted pacemakers in the Netherlands, 1984-1997; number, types and patient characteristics].

OBJECTIVE: To carry out a survey of the numbers of patients in the Netherlands who received a pacemaker in 1984-1997 and the types of pacemaker. DESIGN: Retrospective, descriptive. METHOD: Information on pacemaker patients and pacemakers in the Netherlands during the years 1984-1997 was obtained from the Dutch Pacemaker Patient Registration organisation and those in 15 other West-European countries from the European Working Group on Cardiac Pacing. Both organisations use the European Pacemaker Identification Card. Demographic information was collected via Statistics Netherlands. RESULTS: In the Netherlands, 23 and 28 primo-implantations/100,000 inhabitants were carried out in 1984 and 1997 respectively. The increase was primarily due to a higher number of implants in people > 65 years of age. The 1997 implant figures were lower than the average in Western Europe (34/100,000). In 1997 there was no difference in gender, mean age at the time of first implant, indications and aetiology between the Netherlands and Western Europe. With respect to the choice of type of pacemaker implanted--VVI(R) or DDD(R)-in Western Europe, the Netherlands lay in the middle. Between 1984 and 1997, the number of Dutch centres with 1-25 implants/year decreased while the number with 51-130 implants/year increased. CONCLUSION: In 1997 the number of primo-implantations at Dutch centres increased in comparison with 1984, but less than the West European average. Implants were increasingly performed in high-volume centres.

Age Factors↗

Excessive urinary albumin levels are associated with future cardiovascular mortality in postmenopausal women.

BACKGROUND: Microalbuminuria is an early predictor of cardiovascular morbidity and mortality, in both diabetic patients and hypertensive patients. Little is known about the relation of microalbuminuria to cardiovascular disease in women of the general population. METHODS AND RESULTS: We have studied the relation of urinary albumin levels to cardiovascular mortality in a cohort study of 12 239 postmenopausal women living in Utrecht, the Netherlands. The initial age was between 52 and 67 years. Women were followed on vital status between 1976 and 1995 (168 513 women-years). Albumin was determined in the urine of 561 cases and 557 controls. Data were analyzed by using a nested case-control design. The cardiovascular mortality rate (95% CI) for women who were in the highest quintile of urinary albumin levels was 13.2/1000 years (8.1 to 20.9) compared with 2.6/1000 years (2.3 to 3.1) in women without detectable urinary albumin. The age-adjusted rate ratio (95% CI) between these groups was 4.4 (2.6 to 7.6). CONCLUSIONS: This is the first large cohort study that confirms a predictive role of urinary albumin for the risk of future cardiovascular mortality independent of hypertension and diabetes. Our findings support the hypothesis that microalbuminuria is a reflection of vascular damage and a marker of early arterial disease in women from the general population.

Age Factors↗

Less medical intervention after sharp demarcation of Grade 1-2 cervical intraepithelial neoplasia smears by neural network screening.

BACKGROUND: Neural network technology has been used for the daily screening of cervical smears in The Netherlands since 1992. The authors believe this method might have the potential to demarcate diagnoses of Grade 1-2 cervical intraepithelial neoplasia (CIN 1-2). METHODS: Of 133,196 women who were screened between 1992-1995, there were 2236 CIN 1-2 smears; 1128 of which were detected by means of neural network screening (NNS) (n = 83,404 women) and 1108 of which were diagnosed by conventional screening (n = 49,792 women). Cytologic and clinical outcomes (first cytologic or histologic follow-up diagnosis) were retrieved for all the women in the study population (n = 1920). Stratification based on clinical outcome resulted in the cases being grouped as overdiagnosed, concordant, or underdiagnosed. The smears were performed by general practitioners, whereas the biopsies were obtained by gynecologists. RESULTS: The prevalence rate for CIN 1-2 was 1.15% (95% confidence interval [95% CI], 1.08-1.23%) for NNS and 1.92% (95% CI, 1.80-2.04%) for conventional diagnosis (P < 0.001). Concordance with histology was significantly higher for NNS (53.9%; 95% CI, 50.7-57.0%) compared with conventional screening (29.2%; 95% CI, 26.4-32.2%). In addition, overdiagnosis was significantly lower for cases diagnosed by NNS (39.4%; 95% CI, 36.3-42.4%) compared with cases diagnosed by conventional screening (62.4%; 95% CI, 59.3-65.5%). CONCLUSIONS: Neural network-based screening can lead to fewer women being burdened unnecessarily with a cytologic diagnosis of CIN 1-2 by resulting in a sharp demarcation in these diagnoses and a corresponding reduction in unnecessary medical interventions. [See editorial on pages 171-172, this issue.]

Cytogenetic Analysis↗

Methylenetetrahydrofolate reductase 677 C/T genotype and cardiovascular disease mortality in postmenopausal women.

Methylenetetrahydrofolate reductase (MTHFR) is involved in the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. A 677 C/T single nucleotide polymorphism localized in the MTHFR gene is associated with both thermolability and reduced activity of the enzyme and is associated with increased homocysteine levels. The authors investigated the relation between the MTHFR 677 C/T polymorphism and risk of cardiovascular disease mortality in a cohort study of 12,239 women initially aged 52--67 years with a maximum follow-up time of 18 years (1976--1995; 153,732 woman-years of follow-up). The cardiovascular disease mortality rate was highest among women with the MTHFR 677 CC wild-type genotype and lowest among MTHFR 677 TT homozygotes. In comparison with women with the 677 CC wild-type genotype, age-adjusted rate ratios were 0.7 (95% confidence interval: 0.5, 0.9) for 677 CT heterozygotes and 0.6 (95% confidence interval: 0.4, 1.0) for 677 TT homozygotes. The possibility that this relation is a chance finding must be considered, because the relation is weak and of borderline significance. However, it provides an important argument against the view that increased levels of homocysteine directly raise cardiovascular disease risk.

Age Distribution↗