Showing papers by "Diederick E. Grobbee published in 2005"
TL;DR: A multicenter, randomized trial comparing open repair with endovascular repair in 351 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable candidates for both techniques.
Abstract: Background Two randomized trials have shown better outcomes with elective endovascular repair of abdominal aortic aneurysms than with conventional open repair in the first month after the procedure. We investigated whether this advantage is sustained beyond the perioperative period. Methods We conducted a multicenter, randomized trial comparing open repair with endovascular repair in 351 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable candidates for both techniques. Survival after randomization was calculated with the use of Kaplan–Meier analysis and compared with the use of the log-rank test on an intention-to-treat-basis. Results Two years after randomization, the cumulative survival rates were 89.6 percent for open repair and 89.7 percent for endovascular repair (difference, –0.1 percentage point; 95 percent confidence interval, –6.8 to 6.7 percentage points). The cumulative rates of aneurysm-related death were 5.7 percent...
862 citations
TL;DR: Higher testosterone and SHBG levels in aging males are independently associated with a higher insulin sensitivity and a reduced risk of the metabolic syndrome, independent of insulin levels and body composition measurements, suggesting that these hormones may protect against the development of metabolic syndrome.
Abstract: Background: Sex hormone levels in men change during aging. These changes may be associated with insulin sensitivity and the metabolic syndrome. Methods:Westudiedtheassociationbetweenendogenoussex hormones and characteristics of the metabolic syndrome in 400 independently living men between 40 and 80 yr of age in a crosssectionalstudy.Serumconcentrationsoflipids,glucose,insulin, total testosterone (TT), SHBG, estradiol (E2), and dehydroepiandrosterone sulfate (DHEA-S) were measured. Bioavailable testosterone (BT) was calculated using TT and SHBG. Body height, weight, waist-hip circumference, blood pressure, and physical activity were assessed. Smoking and alcohol consumption was estimated from self-report. The metabolic syndrome was defined according to the National Cholesterol Education Program definition, and insulin sensitivity was calculated by use of the quantitative insulin sensitivity check index. Results: Multiple logistic regression analyses showed an inverse relationship according to 1 SD increase for circulating TT [odds ratio (OR) 0.43; 95% confidence interval (CI), 0.32– 0.59], BT (OR 0.62; 95% CI, 0.46–0.83), SHBG (OR 0.46; 95% CI, 0.33–0.64), and DHEA-S (OR 0.76; 95% CI, 0.56–1.02) with the metabolic syndrome. Each SD increase in E2 levels was not significantly associated with the metabolic syndrome (OR 1.16; 95% CI, 0.92–1.45). Linear regression analyses showed that higher TT, BT, and SHBG levels were related to higher insulin sensitivity; -coefficients (95% CI) were 0.011 (0.008– 0.015), 0.005 (0.001–0.009), and 0.013 (0.010–0.017), respectively, whereas no effects were found for DHEA-S and E2. Estimates were adjusted for age, smoking, alcohol consumption, and physical activity score. Further adjustment for insulin levels and body composition measurements attenuated the estimates, and the associations were similar in the group free of cardiovascular disease and diabetes. Conclusions: Higher testosterone and SHBG levels in aging males are independently associated with a higher insulin sensitivity and a reduced risk of the metabolic syndrome, independent of insulin levels and body composition measurements, suggesting that these hormones may protect against the development of metabolic syndrome. (J Clin Endocrinol Metab 90: 2618–2623, 2005)
452 citations
TL;DR: Increasing the intake of fiber in Western populations, where intake is far below recommended levels, may contribute to the prevention of hypertension.
Abstract: Background: Dietary fiber is part of a healthy diet and may exert a protective effect in the cardiovascular system. The effect of fiber intake on blood pressure (BP) has not yet been established. Methods: We performed a meta-analysis of randomized placebo-controlled trials to estimate the effect of fiber supplementation on BP overall and in population subgroups. Original articles published between January 1, 1966, and January 1, 2003, were retrieved for 24 trials that fulfilled criteria for meta-analysis. Data were abstracted on fiber dose, fiber type, BP changes, study design features, and study population characteristics. A random-effects model was used for meta-analysis. Results: Fiber supplementation (average dose, 11.5 g/d) changed systolic BP by –1.13 mm Hg (95% confidence interval: –2.49 to 0.23) and diastolic BP by –1.26 mm Hg (–2.04 to –0.48). Reductions in BP tended to be larger in older (40 years) and in hypertensive populations than in younger and in normotensive ones. Conclusion: Increasing the intake of fiber in Western populations, where intake is far below recommended levels, may contribute to the prevention of hypertension.
378 citations
TL;DR: Unrecognized heart failure is very common in elderly patients with stable chronic obstructive pulmonary disease, and closer co-operation among general practitioners, pulmonologists, and cardiologists is necessary to improve detection and adequate treatment of heart failure in this large patient population.
Abstract: Aims To establish the prevalence of unrecognized heart failure in elderly patients with a diagnosis of chronic obstructive pulmonary disease, in a stable phase of their disease.
Methods and results In a cross-sectional study, patients ≥65 years of age, classified as having chronic obstructive pulmonary disease by their general practitioner and not known with a cardiologist-confirmed diagnosis of heart failure, were invited to our out-patient clinic. Four hundred and five participants underwent an extensive diagnostic work-up, including medical history and physical examination, followed by chest radiography, electrocardiography, echocardiography, and pulmonary function tests. As reference (i.e. ‘gold’) standard the consensus opinion of an expert panel was used. The panel based the diagnosis of heart failure on all available results from the diagnostic assessment, guided by the diagnostic principles of the European Society of Cardiology (ESC) for heart failure (i.e., symptoms and echocardiographic systolic and/or diastolic dysfunction). The diagnosis of chronic obstructive pulmonary disease was based on the diagnostic criteria of the Global Initiative (GOLD) for chronic obstructive pulmonary disease. Of 405 participating patients with a diagnosis of chronic obstructive pulmonary disease, 83 (20.5%, 95% CI 16.7–24.8) had previously unrecognized heart failure (42 patients systolic, 41 ‘isolated’ diastolic, and none right-sided heart failure). In total, 244 (60.2%) patients had chronic obstructive pulmonary disease according to the GOLD criteria and 50 (20.5%, 95% CI 15.6–26.1) patients combined with unrecognized heart failure.
Conclusion Unrecognized heart failure is very common in elderly patients with stable chronic obstructive pulmonary disease. Closer co-operation among general practitioners, pulmonologists, and cardiologists is necessary to improve detection and adequate treatment of heart failure in this large patient population.
375 citations
TL;DR: Mortality after surgery is substantial and an association was established between perioperative coma and death and anesthesia management factors like intraoperative presence of anesthesia personnel, administration of drugs intraoperatively and postoperatively, and characteristics of delivered intraoperative and postoperative anesthetic care.
Abstract: Background: Quantitative estimates of how anesthesia management impacts perioperative morbidity and mortality are limited. The authors performed a study to identify risk factors related to anesthesia management for 24-h postoperative severe morbidity and mortality. Methods: A case-control study was performed of all patients undergoing anesthesia (1995-1997). Cases were patients who either remained comatose or died during or within 24 h of undergoing anesthesia. Controls were patients who neither remained comatose nor died during or within 24 hours of undergoing anesthesia. Data were collected by means of a questionnaire, the anesthesia and recovery form. Odds ratios were calculated for risk factors, adjusted for confounders. Results: The cohort comprised 869,483 patients; 807 cases and 883 controls were analyzed. The incidence of 24-h postoperative death was 8.8 (95% confidence interval, 8.2-9.5) per 10,000 anesthetics. The incidence of coma was 0.5 (95% confidence interval, 0.3-0.6). Anesthesia management factors that were statistically significantly associated with a decreased risk were: equipment check with protocol and checklist (odds ratio, 0.64), documentation of the equipment check (odds ratio, 0.61), a directly available anesthesiologist (odds ratio, 0.46), no change of anesthesiologist during anesthesia (odds ratio, 0.44), presence of a full-time working anesthetic nurse (odds ratio, 0.41), two persons present at emergence (odds ratio, 0.69), reversal of anesthesia (for muscle relaxants and the combination of muscle relaxants and opiates; odds ratios, 0.10 and 0.29, respectively), and postoperative pain medication as opposed to no pain medication, particularly if administered epidurally or intramuscularly as opposed to intravenously. Conclusions: Mortality after surgery is substantial and an association was established between perioperative coma and death and anesthesia management factors like intraoperative presence of anesthesia personnel, administration of drugs intraoperatively and postoperatively, and characteristics of delivered intraoperative and postoperative anesthetic care.
351 citations
TL;DR: Age-adjusted mortality is reduced 2% with each increasing year of age at menopause, and ischemic heart disease mortality is 2% lower, although the risk of death from uterine or ovarian cancer is increased by 5%, the net effect of a later menoppause is an increased lifespan.
Abstract: BACKGROUND: A later menopause has been associated with a decreased cardiovascular risk but with an increased risk for breast and endometrial cancer. The net effect on mortality is unclear. We determined the association of age at menopause with longevity and with the balance between cardiovascular and cancer mortality. METHODS: We analyzed data from a breast cancer screening cohort comprising 12,134 postmenopausal women followed for an average of 17 years. We used Cox proportional hazards models and life tables to calculate the life expectancy of an average Dutch woman at age 50. RESULTS: During 204,024 person-years, there were 2607 deaths, of which 963 were due to cardiovascular diseases and 812 due to cancer. Ischemic heart disease risk decreased with a later menopause (hazard ratio [HR] = 0.98 per year; 95% confidence interval = 0.96-0.99), but the risk of fatal uterine or ovarian cancer increased (1.07 per year; 1.01-1.12). A later menopause was associated with longer overall survival; HR for total mortality was 0.98 per year (0.97-0.99). Life expectancy in women with menopause after age 55 was 2.0 years longer than those with menopause before age 40. Adjustment for potential confounders did not materially change the results. CONCLUSIONS: Age-adjusted mortality is reduced 2% with each increasing year of age at menopause. In particular, ischemic heart disease mortality is 2% lower. Although the risk of death from uterine or ovarian cancer is increased by 5%, the net effect of a later menopause is an increased lifespan.
343 citations
TL;DR: In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function, which may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state.
Abstract: Context: Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly. Objective: We determined to what extent thyroid hormone concentrations are related to physical function and mortality in elderly men. Design: A longitudinal population study (the Zoetermeer study) was conducted. Mortality was registered in the subsequent 4 yr. Participants: Four hundred three independently and ambulatory living men (aged 73–94 yr) participated. Main Outcome Measures: The study examined the association between serum thyroid hormones and parameters of physical function as well as the association with mortality.
258 citations
TL;DR: A limited number of items easily available from history and physical examination, with addition of NT-proBNP and electrocardiography, can help general practitioners to identify concomitant heart failure in individual patients with stable COPD.
Abstract: Objective To determine which clinical variables provide diagnostic information in recognising heart failure in primary care patients with stable chronic obstructive pulmonary disease (COPD) and whether easily available tests provide added diagnostic information. Design Cross sectional diagnostic study. Setting 51 primary care practices. Participants 1186 patients aged 65 years with COPD diagnosed by their general practitioner who did not have a diagnosis of heart failure confirmed by a cardiologist. Main outcome measures Independent diagnostic variables for concomitant heart failure in primary care patients with stable COPD. Results 405 patients (34% of eligible patients) underwent a systematic diagnostic investigation, which resulted in 83 (20.5%) receiving a new diagnosis of concomitant heart failure. Independent clinical variables for concomitant heart failure were a history of ischaemic heart disease, high body mass index, laterally displaced apex beat, and raised heart rate (area under the receiver operating characteristic curve (ROC area) 0.70, 95% confidence interval 0.64 to 0.76). Addition of measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) to the reduced “clinical model” had the largest added diagnostic value, with a significant increase of the ROC area to 0.77 (0.71 to 0.83), followed by electrocardiography (0.75, 0.69 to 0.81). C reactive protein and chest radiography had limited added value. A simplified diagnostic model consisting of the four independent clinical variables plus NT-proBNP and electrocardiography was developed. Conclusions A limited number of items easily available from history and physical examination, with addition of NT-proBNP and electrocardiography, can help general practitioners to identify concomitant heart failure in individual patients with stable COPD.
220 citations
TL;DR: Only in populations at low risk, endothelial function measured by FMD is related to the principal cardiovascular risk factors, and to the estimated 10-year risk of CHD.
198 citations
TL;DR: Apparent curvilinear associations between T and certain cognitive functions in men suggest an optimal hormone level for particular cognitive tasks and are explained by linear associations in the oldest age category.
Abstract: Objective: To determine whether endogenous sex hormone levels are associated with cognitive functioning in men. Methods: Cognitive performance was assessed in 400 independently living men between ages 40 and 80 in a population-based cross-sectional study. Compound scores were calculated for memory function, processing capacity/speed, and executive function. The Mini-Mental State Examination was used as a measure of global cognitive function. The adjusted association of testosterone (T) and estradiol (E2) (total, bioavailable) with neuropsychological test scores in the total group and in subgroups was assessed by linear and logistic regression analysis. Results: Curvilinear associations were observed between T and memory performance and processing capacity/speed, suggesting optimal sex hormone levels. No association between E2 and cognitive functioning was found. After the population was subdivided into four age decades, a linear association of T with cognitive functioning in the oldest age category remained. No association was found in the other age decades. Lower bioavailable T levels were associated with lower scores on processing capacity/speed and executive function; (95% CI) values were 0.36 (0.07 to 0.66) and 0.17 (0.01 to 0.35). Similar results were observed for total T. Conclusions: Higher testosterone (T) levels are associated with better cognitive performance in the oldest age category. Apparent curvilinear associations between T and certain cognitive functions in men suggest an optimal hormone level for particular cognitive tasks and are explained by linear associations in the oldest age category.
154 citations
TL;DR: Early house dust mite and cat allergen exposure might lead to sensitization and, in case of cat allERgen exposure, to persistent wheeze, respectively, but only in subgroups defined by maternal atopy.
Abstract: Background The relationship between mite and pet allergen exposure in infancy and the subsequent development of sensitization and asthma is complex. Objective We prospectively investigated the effect of allergen exposure at 3 months of age on the development of sensitization, wheeze, and physician-diagnosed asthma in the first 4 years of life in a birth cohort of children with and without an atopic mother. Methods Children participated in the Prevention and Incidence of Asthma and Mite Allergy study. Allergen exposure at 3 months of age was determined from mattress dust samples. Specific IgE to inhalant allergens was measured at 4 years of age, and information about wheeze and physician-diagnosed asthma was collected with yearly questionnaires. Results Mite and cat allergen exposure in infancy were associated with an increased risk of specific sensitization to house dust mite and cat, respectively, at 4 years of age. There were borderline significant associations between cat allergen exposure and persistent wheeze in the total study population and between dog allergen exposure and persistent wheeze in children with a nonatopic mother. In children with an atopic mother, there was some indication of a positive association between mite allergen exposure and physician-diagnosed asthma. Conclusion Early house dust mite and cat allergen exposure might lead to sensitization and, in case of cat allergen exposure, to persistent wheeze. Early mite and dog allergen exposure might lead to asthma and persistent wheeze, respectively, but only in subgroups defined by maternal atopy.
TL;DR: The onset of joint bleeding is inversely related with treatment requirement and arthropathy and may serve as an indicator of clinical phenotype, providing a starting point for aetiological research and individualization of treatment.
Abstract: To quantify variation in clinical phenotype of severe haemophilia we performed a single centre cohort study among 171 severe haemophilia patients. Age at first joint bleed, treatment requirement (i.e. annual clotting factor use), annual bleeding frequency and arthropathy were documented. Because treatment strategies intensified during follow-up, patients were stratified in two age groups: patients born 1968-1985 (n = 91), or 1985-2002 (n = 80). A total of 2166 patient-years of follow-up were available (median 12.0 years per patient). Age at first joint bleed ranged from 0.2 to 5.8 years. Patients who had their first joint bleed later needed less treatment and developed less arthropathy. In patients born 1968-1985 during both on-demand and prophylactic treatment, the 75th percentile of annual joint bleed frequency was consistently four times as high as the 25th percentile. In both age groups variation in annual clotting factor use between 25th and 75th percentiles was 1.4-1.5 times for prophylaxis and 3.8 times for on-demand treatment. To conclude, the onset of joint bleeding is inversely related with treatment requirement and arthropathy and may serve as an indicator of clinical phenotype. Thus, providing a starting point for aetiological research and individualization of treatment.
TL;DR: Carotid artery stiffness is no independent risk factor for vascular events in patients with manifest arterial disease, however, in patients who differ with respect to baseline vascular risk, arterial stiffness, or systolic blood pressure, decreased stiffness may indicate a decreased risk of vascular events.
Abstract: Aims To study whether arterial stiffness is related to risk of new vascular events in patients with manifest arterial disease and to examine whether this relation varies between patients who differ with respect to baseline vascular risk, arterial stiffness, or systolic blood pressure (SBP).
Methods and results The study was performed in the first consecutive 2183 patients with manifest arterial disease enrolled in the SMART study (Second Manifestations of ARTerial disease), a cohort study among patients with manifest arterial disease or cardiovascular risk factors. Common carotid distension (i.e. the change in carotid diameter in systole relative to diastole) was measured at baseline by ultrasonography. With the distension, several stiffness parameters were determined. In the entire cohort, none of the carotid artery stiffness parameters was related to the occurrence of vascular events. However, decreased stiffness was related to decreased vascular risk in subjects with low baseline SBP. The relation of carotid stiffness with vascular events did not differ between tertiles of baseline risk and carotid stiffness.
Conclusion Carotid artery stiffness is no independent risk factor for vascular events in patients with manifest arterial disease. However, in patients with low SBP, decreased carotid stiffness may indicate a decreased risk of vascular events.
TL;DR: In Europe, community awareness of HF is low and the general public is unlikely to demand appropriate measures by healthcare authorities and providers, so strategies to educate the public about HF are needed.
Abstract: Aims Appropriate heart failure (HF) care and adequate resourcing require recognition of its clinical, social, and economic importance by the general public besides healthcare authorities and providers. The extent of public awareness in Europe is not known. Methods and results A total of 7958 subjects were randomly selected from nine European countries (minimum 100/group per country). Each completed a 32-question survey on HF covering recognition, impact on health, comparative prevalence and severity, treatment, and costs. Although 86% of respondents had heard of HF, only 3% could correctly identify HF from a description of typical symptoms and signs, 31% correctly identified angina, and 51% identified transient ischaemic attack/stroke. Only 29% thought that HF signs and symptoms indicate a 'severe' condition. Most thought that HF patients should reduce all physical activity and 34% believed HF a normal consequence of ageing. Sixty-seven per cent thought that HF patients live longer than cancer patients. Only 9% believed that HF leads to greater healthcare expenditure than cancer, HIV, or diabetes. Overall, responses were comparable between countries. Conclusion In Europe, community awareness of HF is low. Therefore, the general public is unlikely to demand appropriate measures by healthcare authorities and providers. A better understanding of HF could improve its prevention and management. Strategies to educate the public about HF are needed.
TL;DR: Levels of estrogens and dehydroepiandrosterone sulfate are higher in women who consume more alcohol, which supports the hypothesis that alcohol use may increase breast cancer risk at least partially through an effect on sex steroid levels.
Abstract: Breast cancer risk increases with increased levels of alcohol consumption, potentially through an effect on sex hormone levels. In a cross-sectional study among Dutch participants (n = 17,357) of the European Prospective Investigation into Cancer and Nutrition conducted in Utrecht, The Netherlands (Prospect-EPIC), we investigated the relation between alcohol intake and estrogen and androgen levels. Alcohol intake was calculated from a food frequency questionnaire. Women were included if they were postmenopausal, had donated a blood sample, and did not use hormone replacement therapy or oral contraceptives at the time of blood donation (n = 1093). Women who consumed more than 25 g of alcohol per day had higher levels of estrone (P(trend) = 0.001), estradiol (P(trend) = 0.03), dehydroepiandrosterone sulfate (P(trend) = 0.18), and higher estrone/estradiol (P(trend) = 0.14) and estrone/androstenedione (P(trend) = 0.06) ratios, compared with nondrinkers. Levels of androstenedione, testosterone, and SHBG did not differ between women who consumed alcohol and nondrinkers. Furthermore, there were no differences in the free androgen index or estradiol to testosterone ratio. In conclusion, levels of estrogens and dehydroepiandrosterone sulfate are higher in women who consume more alcohol. This finding supports the hypothesis that alcohol use may increase breast cancer risk at least partially through an effect on sex steroid levels.
TL;DR: MRI correlated more strongly with mean IQ and median TIS than ultrasound and Subtle white matter lesions are better detected with MRI which could explain the stronger correlation with IQ and motor performance.
Abstract: Aim: To examine the correlation between neonatal cranial ultrasound and school age magnetic resonance imaging (MRI) and neurodevelopmental outcome. Methods: In a prospective 2 year cohort study, 221 children (gestational age ⩽32 weeks and/or birth weight ⩽1500 g) participated at a median age of 8.1 years (inclusion percentage 78%). Conventional MRI, IQ (subtests of the WISC), and motor performance (Movement Assessment Battery for Children) at school age were primary outcome measurements. Results: Overall, there was poor correspondence between ultrasound group classifications and MRI group classifications, except for the severe group (over 70% agreement). There was only a 1% chance of the children with a normal cranial ultrasound having a major lesion on MRI. Mean IQ (standard deviation) was significantly lower in children with major ultrasound or MRI lesions, but was also lower in children with minor lesions on MRI compared to children with a normal MRI (91±16, 100±13, 104±13 for major lesions, minor lesions, and normal MRI, respectively). Median total impairment score (TIS) was significantly higher in children with major lesions on ultrasound or MRI as well as in children with minor lesions on MRI (TIS 4.0 and 6.25 for normal and minor lesions on MRI, respectively; p Conclusions: A normal neonatal cranial ultrasound excluded a severe lesion on MRI in 99% of cases. MRI correlated more strongly with mean IQ and median TIS than ultrasound. Subtle white matter lesions are better detected with MRI which could explain the stronger correlation of MRI with IQ and motor performance.
TL;DR: Compared with previous studies, the influence of BMI on relative density was completely due to an effect on nondense tissue, and inferences about the etiology of breast density should be made on the basis of absolute measures.
Abstract: Breast density, as visible on mammograms, is generally assessed as the occupied percentage of the breast and is a risk factor for breast cancer. Various studies have looked into the causation and alteration of relative density but the relation of a determinant with a relative measure does not allow a direct etiologic interpretation. It was our goal to compare the effects of known determinants on relative density and the absolute amounts of dense and nondense tissues. We measured the absolute and relative densities in a population of 418 postmenopausal women participating in a breast cancer screening program. The occupied surface area was calculated after manually tracing the contours of the tissues on digitized mammograms. Information on determinants was available through physical examination and questionnaires. Data were analyzed by multivariate linear regression. Age and parity were found to decrease the amount of dense tissue and the ages at menarche and menopause were found to increase it (R(2) = 13%). The amount of nondense tissue was increased by higher body mass index (BMI), age, and parity (R(2) = 43%). Relative density was affected by a combination of these factors (R(2) = 29%) with directionalities of effects that are comparable to those of dense tissue. However, the magnitudes of these effects were the resultant of the effects on dense and nondense tissues. The influence of BMI on relative density was completely due to an effect on nondense tissue. Although relative density is a relevant prognostic factor, inferences about the etiology of breast density should be made on the basis of absolute measures.
TL;DR: Among patients with severe hemophilia, treated prophylactically with clotting factor, those with a shorter factor VIII half-life required slightly more clotting factors to prevent joint bleeds and subsequent arthropathy than similar patients with a longer factor VIIIHalf-life.
Abstract: BACKGROUND AND OBJECTIVES: Patients with severe hemophilia A have considerably different factor VIII half-lives. Whether this is associated with their clinical characteristics has not been reported. The aim of this study was to describe the association of factor VIII half-lives with treatment and clinical characteristics of patients with severe hemophilia A, who have been treated with individually tailored prophylaxis. DESIGN AND METHODS: Patients were selected from a single-center cohort of 214 patients with severe hemophilia, born between 1944 and 1995. To improve efficiency we measured factor VIII half-life in 42 patients selected from the extremes of the distribution of phenotypes of severe hemophilia. We assessed information on life-long joint bleeds and clotting factor consumption. Orthopedic outcome was assessed by the Pettersson score. RESULTS: Among these patients with severe hemophilia, factor VIII half-life ranged from 7.4-20.4 hours (median 11.8 hours). A one-hour increase in factor VIII half-life was associated with 96 (95% confidence interval (CI) 2 -190) IU less clotting factor use per kg per year. Age was an important determinant of factor VIII half-life, and explained a large part of the association between factor VIII half-life and clotting factor consumption. The median number of joint bleeds per year and arthropathy were similar for patients with different half-lives. INTERPRETATION AND CONCLUSIONS: Among patients with severe hemophilia, treated prophylactically with clotting factor, those with a shorter factor VIII half-life required slightly more clotting factor to prevent joint bleeds and subsequent arthropathy than similar patients with a longer factor VIII half-life.
TL;DR: The Utrecht Health Project combines key elements of traditional epidemiologic cohort studies with the current power of routine electronic medical record keeping in primary care to optimizes routine health care data for use in scientific research.
Abstract: Background
Research on the impact of changes in healthcare policy, developments in community and public health and determinants of health and disease during lifetime may effectively make use of routine healthcare data. These data, however, need to meet minimal criteria for quality and completeness. Research opportunities are further improved when routine data are supplemented with a standardized ‘baseline’ assessment of the full population. This formed the basis for a new study initiated in a newly developed large residential area in Leidsche Rijn, part of the city of Utrecht, the Netherlands.
TL;DR: It is concluded that using the CIMT-to-lumen ratio yields the weakest associations and other approaches for adjustment for common carotid lumen diameter do not affect the magnitude or precision of the association of common CimT to risk of AMI.
Abstract: Background— It has been argued that lumen diameter of the common carotid artery should be taken into account in analyses on common carotid intima-media thickness (CIMT) and cardiovascular risk. Yet, no published report has dealt with this issue in detail. Methods— In the Rotterdam study baseline ultrasound images of the carotid arteries were made. During follow-up of 8.2 years, 656 new acute myocardial infarctions (AMI) occurred. Regression analysis was used to study myocardial infarction relation to right (or left) common CIMT with various adjustments for right-, or left-sided lumen diameter. Lumen adjustment was made by (1) a simple adjustment in a regression equation; (2) using the CIMT-to-lumen ratio; (3) using arterial mass, calculated as ({π×[(lumen+near wall CIMT+far wall CIMT)/2]2}−[π×(lumen/2)2]). Results— AMI disease risk increased per standard deviation increase in common CIMT (0.177 mm): hazard ratio (HR) 1.28 (95% CI, 1.19 to 1.37). When lumen diameter was taken into account the HR was 1.26 (...
TL;DR: Higher serum ferritin concentrations in postmenopausal women are associated with an increased risk of ischemic stroke, but neither serum iron nor transferrin saturation was associated with a increased stroke risk.
Abstract: Background and Purpose— Iron is an essential element for the human body. It has, however, been suggested that excessive iron stores may increase the risk of vascular disease. So far, epidemiologic studies on stroke are sparse. Methods— We studied the association between iron status and stroke risk in a population-based cohort of 11 471 Dutch postmenopausal women between 49 and 70 years of age. Women were included between 1993 and 1997 and followed up until January 1, 2000, for cerebrovascular events. We conducted a case-cohort study by using all stroke cases (n=63) and a random sample of the baseline cohort (n=1134). Serum ferritin, serum iron, and transferrin saturation were measured as markers of iron status. A weighted Cox proportional-hazards model was used to estimate crude and multivariate-adjusted hazard ratios for tertiles of different iron parameters in relation to stroke. Results— In a multivariate model, the highest tertile of serum ferritin concentration was associated with an increased risk o...
TL;DR: To investigate whether levels of endogenous hormones, in particular circulating oestrogens and SHBG, are associated with cognition in healthy postmenopausal women, a large number of women with normal levels of these hormones are surveyed.
Abstract: Summary Objective To investigate whether levels of endogenous hormones, in particular circulating oestrogens and SHBG, are associated with cognition in healthy postmenopausal women Design Cross-sectional study Patients Four hundred and two healthy postmenopausal women aged 50‐74 years between 8 and 30 years after menopause, none taking oestrogen Measurements Serum concentration of oestradiol, oestrone, and sex hormone binding globulin (SHBG) determined by immunoassay Cognition assessed using the mini-mental state examination questionnaire (MMSE) Results In this group, 149 individuals had a MMSE score < 27, while only 89 individuals had a MMSE score < 26, indicating a relatively healthy population with regard to cognitive ability Cognition decreased with age, time since menopause and blood pressure, and was better with higher age at menopause Serum oestrogens and SHBG levels were not related to age, age at menopause, or time since menopause, and oestrogen levels were positively associated with blood pressure After adjustment for mean arterial pressure and SHBG, the frequency of mild cognitive impairment decreased significantly with higher oestradiol and oestrone serum levels [ORs Q5 vs Q1: 0·41 (95% CI 0·20 ‐ 0·84) and 0·51 (95% CI 0·20 ‐ 0·99) for oestradiol and oestrone, respectively] Conclusions Postmenopausal women with higher remaining circulating oestradiol levels appear less likely to suffer from cognitive impairment This effect is independent of age at menopause, time since menopause and BMI These findings support the hypothesis that endogenous oestrogens may protect against cognitive decline with ageing
TL;DR: This study is one of the few large-scale epidemiological studies among 4-yr-old children from the general population showing that children with symptoms of asthma and atopy have higher levels of exhaled nitric oxide than those without.
Abstract: Airway inflammation is an early feature of asthma. Early detection and anti-inflammatory treatment may have important therapeutic impact. Exhaled nitric oxide is a noninvasive marker of airway inflammation. The current study investigated the association between exhaled nitric oxide and asthma, wheezing phenotypes, atopy and blood eosinophilia in a large group of 4-yr-old children from the general population. All children participated in the Prevention and Incidence of Asthma and Mite Allergy study, a birth cohort study of high-risk (atopic mother) and low-risk children in the Netherlands. Nitric oxide levels were successfully determined in 429 children. Although there was overlap in the distribution of values of children with and without asthma or atopy, mean values were higher in children with atopy or doctor's diagnosed asthma (geometric mean (ppb) 9.4 and 10.0, respectively) as compared to those without (7.7 and 7.9). Values were highest in atopic symptomatic children. Values were not associated with wheezing phenotype or blood eosinophilia. This study is one of the few large-scale epidemiological studies among 4-yr-old children from the general population showing that children with symptoms of asthma and atopy have higher levels of exhaled nitric oxide than those without.
TL;DR: It is concluded that in eugonadal men, higher SHBG levels are associated with lower levels of non-SHBG-E2 but slightly higher levels of the E2/T ratio of either total (beta = -0.016 +/- 0.002; P < 0.001) or non- SHBG-bound (beta +0.011 +/-0.002) hormone.
Abstract: Results of in vitro experiments indicate that with increasing concentrations of SHBG, testosterone (T) is preferentially bound to SHBG in comparison with estradiol (E2). In these studies, the ratio of non-SHBG-bound E2 (non-SHBG-E2) to non-SHBG-T increased with increasing levels of SHBG. SHBG has consequently been regarded as an estrogen amplifier. In this cross-sectional study in 399 men aged between 40 and 80 yr we tested whether higher levels of SHBG are associated with a higher estrogen/androgen ratio in vivo. The mean T level of these men was in the eugonadal range [536 +/- 152 ng/dl (18.6 +/- 5.26 nmol/liter), mean +/- sd]. With increasing SHBG levels the non-SHBG-bound fraction of T decreased from 80 to 36% and that of E2 from 89 to 53%. Higher levels of SHBG were associated with higher levels of both total T [regression coefficient (beta) after adjustment for age and body mass index, 286 +/- 15.8; P < 0.001] and total E2 (beta = 4.47 +/- 0.90; P < 0.001). However, SHBG levels were negatively related with levels of non-SHBG-E2 (beta = -1.78 +/- 0.69; P < 0.001), whereas there was a positive association between levels of SHBG and non-SHBG-T (beta = 32.0 +/- 9.78; P = 0.001). Furthermore, we observed a negative relationship between SHBG levels and the E2/T ratio of either total (beta = -0.016 +/- 0.002; P < 0.001) or non-SHBG-bound (beta = -0.011 +/- 0.002; P < 0.001) hormone. Therefore, we conclude that in eugonadal men, higher SHBG levels are associated with lower levels of non-SHBG-E2 but slightly higher levels of non-SHBG-T. This means that SHBG cannot be regarded as an estrogen amplifier in eugonadal men.
TL;DR: The findings support the evidence of a decreased risk of type 2 diabetes with moderate alcohol consumption and expand this to a population of older women.
Abstract: OBJECTIVE - This study aimed to investigate the relation between alcohol consumption and type 2 diabetes among older women. RESEARCH DESIGN AND METHODS - Between 1993 and 1997, 16,330 women aged 49-70 years and free from diabetes were enrolled in one of the Dutch Prospect-EPIC (European Prospective Study Into Cancer and Nutrition) cohorts and followed for 6.2 years (range 0.1-10.1). At enrollment, women filled in questionnaires and blood samples were collected. RESULTS - During follow-up, 760 cases of type 2 diabetes were documented. A linear inverse association (P = 0.007) between alcohol consumption and type 2 diabetes risk was observed, adjusting for potential confounders. Compared with abstainers, the hazard ratio for type 2 diabetes was 0.86 (95% CI 0.66-1.12) for women consuming 5-30 g alcohol per week, 0.66 (0.48-0.91) for 30-70 g per week, 0.91 (0.67-1.24) for 70-140 g per week, 0.64 (0.44-0.93) for 140-210 g per week, and 0.69 (0.47-1.02) for >210 g alcohol per week. Beverage type did not influence this association. Lifetime alcohol consumption was associated with type 2 diabetes in a U-shaped fashion. CONCLUSIONS - Our findings support the evidence of a decreased risk of type 2 diabetes with moderate alcohol consumption and expand this to a population of older women. © 2005 by the American Diabetes Association.
TL;DR: The OM-6 appears to be the best available instrument to assess functional health status in children with OM in a research setting, however, the lack of true HRQoL instruments as well as incomplete data on their reliability and validity, limit both the current knowledge of HRZoL in OM and the application of current instruments in both research and clinical practice.
TL;DR: The results of this study suggest that the Pvu II polymorphism in the ER-α, or another mutation in linkage disequilibrium with PvuII, in combination with high E2 levels increases breast cancer risk in postmenopausal women.
Abstract: Objective: In this study we aimed to investigate whether the PvuII, XbaI and B-variant polymorphisms in the estrogen receptor α gene (ER-α) are associated with an increased risk of breast cancer in postmenopausal women, and whether the effect of high estradiol (E2) levels on breast cancer risk is altered by these polymorphisms. The selection of these polymorphisms was based on previously published associations with osteoporosis and spontaneous abortions.
TL;DR: The results of this study indicate that increased arterial stiffness may interfere with valid measurement of FMD and that patients with stiff arteries may be considered for exclusion from analyses involving FMD to ensure its validity.
TL;DR: Among women who underwent natural menopause, a higher number of menstrual cycles in lifetime, reflecting a longer exposure to endogenous estrogens, is associated with an increased breast cancer risk.
Abstract: Objective: To explore whether the lifetime cumulative number of menstrual cycles, as an index for total exposure to endogenous estrogens, and the number of menstrual cycles until a first full-term pregnancy (FFTP), are associated with breast cancer risk in postmenopausal women. Methods: Population-based study with data from the Prospect-European Prospective Investigation into Cancer and Nutrition study. Naturally menopausal participants were eligible (n = 6,718). The cumulative number of menstrual cycles was computed in 6,031 (90%) women. We calculated the number of cycles until FFTP among parous participants. The number of menstrual cycles was impossible to compute in women who reported to be always irregular; therefore, we added the ‘‘always irregular’’ category in the analysis. During the 46,746 person-years of follow-up, 168 breast cancer cases were identified. Cox regression models were used and adjustments were made to account for potential confounders. Results: Even when our data does not show a clear linear gradient, we observed an increased breast cancer risk in women with a higher number of cumulative menstrual cycles in their lifetime. Using _ 491 cycles was 1.11 (.56, 2.19), 1.88 (1.14, 3.12), 1.74 (1.05, 2.87), and 1.80 (1.09, 2.96), respectively. Although not statistically significant, and of less magnitude, the risk estimates for the number of cycles before FFTP showed the same tendency. Conclusion: Among women who underwent natural menopause, a higher number of menstrual cycles in lifetime, reflecting a longer exposure to endogenous estrogens, is associated with an increased breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2005;14(4):799 – 804)
TL;DR: It is proposed that the presence of climacteric complaints determines the susceptibility to hormone replacement therapy, and epidemiological approaches are suggested to test the hypothesis.
Abstract: There is a large discrepancy between the findings of observational and experimental studies on the effects of post-menopausal hormone therapy (HT) and coronary heart disease risk. Observational studies, mainly comprising peri-menopausal women, report risk reductions up to 30-50%, whereas the experimental studies, comprising elderly women, do not show coronary protection. Suggested explanations are methodological differences, such as confounding or healthy user bias, incomplete capture of early events, the stage of atherosclerosis at the start of HT, formulation or dose of HT, or early susceptibility to thrombotic events. We propose that the presence of climacteric complaints determines the susceptibility to hormone replacement therapy. Climacteric complaints are the main indication for HT in the population, whereas in the clinical trials women with climacteric complaints were either explicitly excluded or comprised only a minority of the total randomized population. There is some, albeit circumstantial evidence to support this hypothesis. Women with climacteric complaints of sweating not only appear to have lower levels of serum oestradiol, but also lose more bone than women without climacteric complaints. Consequently, sweating episodes may indicate potential benefits from HT. It has also been reported that hot flushes during menopause correlate with a higher level of oxidative stress and an increased cardiovascular reactivity to stressful situations. We suggest epidemiological approaches to test our hypothesis.