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Biomedical subjects

Diederick E Grobbee

Publications and source records attributed to Diederick E Grobbee.

214 records · Page 12Linked to original sources

Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials.

OBJECTIVE: The antihypertensive effect of fish oil was estimated from randomized trials using metaregression analysis. Modification of the blood pressure (BP) effect by age, gender, blood pressure, and body mass index was examined. METHODS: A total of 90 randomized trials of fish oil and BP were identified through MEDLINE (1966-March 2001). Trials with co-interventions, patient populations, non-placebo controls, or duration of < 2 weeks were excluded. A total of 36 trials (50 strata) were included, 22 of which had a double-blind design. Original reports were retrieved for data collection on sample size, study design, duration, fish oil dose, BP changes and baseline characteristics of trial populations. Pooled BP estimates were obtained by metaregression analysis, weighted for trial sample sizes. Stratified analyses according to population characteristics were performed. RESULTS: Intake of fish oil was high in most trials (median dose: 3.7 g/day). Fish oil reduced systolic BP by 2.1 mmHg [95% confidence interval (CI): 1.0, 3.2; P < 0.01] and diastolic BP by 1.6 mmHg (95% CI: 1.0. 2.2; P < 0.01). Restricting the analysis to double-blind trials yielded BP reductions of 1.7 mmHg (95% CI: 0.3, 3.1) and 1.5 mmHg (95% CI: 0.6, 2.3), respectively. BP effects tended to be larger in populations that were older (> 45 years) and in hypertensive populations (BP >or= 140/90 mmHg). CONCLUSIONS: High intake of fish oil may lower BP, especially in older and hypertensive subjects. The antihypertensive effect of lower doses of fish oil (< 0.5 g/day) however, remains to be established.

Blood Pressure↗

Arterial stiffness in postmenopausal women: determinants of pulse wave velocity.

OBJECTIVE To investigate the degree and potential cardiovascular determinants of arterial stiffness, assessed by aortic pulse wave velocity (PWV) measurements, and to relate arterial stiffness to absolute 10-12-year risks of stroke, coronary heart disease and death, as estimated by available risk functions, in postmenopausal women. METHOD We performed a cross-sectional study among 385 postmenopausal women, aged 50-74 years, sampled from the general population. Arterial stiffness was assessed non-invasively by measurement of aortic PWV using applanation tonometry. Information on health was obtained by medical history, registration of current medication, and physical examination. Height, weight, waist and hip circumferences, fasting glucose, total and high-density lipoprotein (HDL) cholesterol, triglycerides, resting blood pressure, and heart rate were measured. Three risk scores were used to estimate, for each individual, the absolute risk of stroke, coronary heart disease, and death within 10-12 years as a function of their cardiovascular risk factor profile. The relationship between PWV and these risk scores was subsequently determined. RESULTS Significant positive relationships with PWV were found for body mass index, fasting glucose, diabetes mellitus, and triglycerides in analyses adjusted for age, mean arterial blood pressure, and heart rate. Height and HDL cholesterol were inversely related to PWV. The risks of stroke, coronary heart disease, and death increased with increasing PWV in a linear graded manner. CONCLUSIONS This cross-sectional study among postmenopausal women provides evidence that most of the established cardiovascular risk factors are determinants of aortic PWV. Increased PWV marks an increased risk of stroke, coronary heart disease, and death within 10-12 years.

Aged↗

Carotid intima-media thickness, arterial stiffness and risk of cardiovascular disease: current evidence.

AIMS: Over recent decades the interest in cardiovascular epidemiology has broadened from studies on causes and consequences of elevated cardiovascular risk factors to include research on causes and consequences of atherosclerosis and associated arterial wall abnormalities. One of the underlying reasons was that established cardiovascular risk factors were insufficiently accurate in identifying those individuals who will suffer from cardiovascular disease in the future and measures of subclinical atherosclerosis may enhance the precision of these predictions and thus enable better-tailored medical care to be provided. The usefulness of measuring subclinical atherosclerosis is conditional on evidence that presence of subclinical atherosclerosis confers an increased risk of cardiovascular disease and that favourable changes in subclinical atherosclerosis parallel reductions in risk. We aimed at providing an overview of epidemiological data on carotid intima-media thickness (CIMT) and arterial stiffness measurements and their relation to risk of cardiovascular disease. METHODS: We reviewed the published epidemiological data. RESULTS AND CONCLUSION: CIMT is a good indicator of cardiovascular risk and provides a graded measure of vascular damage: no clear CIMT level above which the cardiovascular risk appears to increase considerably The evidence for arterial stiffness, assessed as carotid distensibility or aortic pulse wave velocity, as an indicator for risk of cardiovascular disease is restricted to subjects with either hypertension or end-stage renal disease or based on small studies in renal transplant patients and elderly. Evidence to indicate that information on carotid intima-media thickness or arterial stiffness, additional to established cardiovascular risk factors, helps to distinguish subjects into those with a high and those with a low absolute risk of cardiovascular disease is limited, but needed. Also, information on the direct comparison of both arterial stiffness measures in their ability to predict cardiovascular disease is needed.

Cardiovascular Diseases↗

A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels.

We investigated whether a polymorphism in codons 22 and 23 of the glucocorticoid (GC) receptor gene [GAGAGG(GluArg) --> GAAAAG(GluLys)] is associated with altered GC sensitivity, anthropometric parameters, cardiovascular risk factors, and sex steroid hormones. In a subgroup of 202 healthy elderly subjects of the Rotterdam Study, we identified 18 heterozygotes (8.9%) for the 22/23EK allele (ER22/23EK carriers). In the highest age group, the number of ER22/23EK carriers was higher (67-82 years, 12.9%) than in the youngest age group (53-67 years, 4.9%; P < 0.05). Two dexamethasone (DEX) suppression tests with 1 and 0.25 mg DEX were performed, and serum cortisol and insulin concentrations were compared between ER22/23EK carriers and noncarriers. After administration of 1 mg DEX, the ER22/23EK group had higher serum cortisol concentrations (54.8 +/- 18.3 vs. 26.4 +/- 1.4 nmol/l, P < 0.0001), as well as a smaller decrease in cortisol (467.0 +/- 31.7 vs. 484.5 +/- 10.3 nmol/l, P < 0.0001). ER22/23EK carriers had lower fasting insulin concentrations (P < 0.001), homeostasis model assessment- insulin resistance (IR) (index of IR, P < 0.05), and total (P < 0.02) and LDL cholesterol concentrations (P < 0.01). Our data suggest that carriers of the 22/23EK allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than noncarriers, resulting in a better metabolic health profile.

Aged↗

Tissue factor pathway inhibitor and other endothelium-dependent hemostatic factors in elderly individuals with normal or impaired glucose tolerance and type 2 diabetes.

OBJECTIVE: Impaired glucose tolerance (IGT) is believed to be a prediabetic phase that precedes the development of type 2 diabetes. In elderly subjects, IGT and diabetes are both independently associated with the occurrence of cardiovascular disease. Endothelial damage precedes atherosclerotic changes of the vascular wall. Therefore, several markers of endothelial dysfunction were examined in elderly subjects with IGT and elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), and thrombomodulin were studied as markers of endothelial dysfunction in a population-based study of elderly subjects with normal glucose tolerance (NGT) or IGT and type 2 diabetes. In addition to these endothelium-dependent factors, we also investigated tissue factor pathway inhibitor (TFPI) activity in relation to metabolic parameters and cardiovascular risk factors. RESULTS: All data were adjusted for age. Increased levels of vWF antigen, t-PA antigen, and PAI-1 activity were seen in the IGT and diabetic group compared with the NGT group. TFPI activity and thrombomodulin levels were increased in all elderly subjects, and no differences were seen between the groups. There was a positive association between HbA(1c) and TFPI activity and vWF antigen. Fasting blood glucose levels correlated with vWF antigen, t-PA antigen, and PAI-1 activity, whereas urine albumin excretion correlated with TFPI activity, vWF antigen, and PAI-1 activity. Serum insulin levels correlated strongly not only with vWF antigen and t-PA antigen but also with PAI-1 activity. This correlation did not change after further adjustment for serum glucose and HbA(1c), which may suggest that in the elderly subjects, impaired fibrinolysis is probably associated with insulin resistance. There were no associations between the endothelium-dependent hemostatic factors and lipids, except for a negative correlation between HDL cholesterol and thrombomodulin. CONCLUSIONS: In elderly subjects with IGT, several endothelium-dependent hemostatic factors are already consistently increased, indicating endothelial damage in this stage.

Aged↗

Cost-utility analysis of patient care in children with meningeal signs.

OBJECTIVES: We designed a model of diagnostic and therapeutic interventions applied in children with meningeal signs. Using this model, we determined in a cost-utility analysis the consequences for society of different diagnostic strategies in terms of quality-adjusted life-years (QALYs) and costs. METHODS: Data were used from 360 children (0.1-15 years) visiting the pediatric emergency department of the Sophia Children's Hospital Rotterdam, The Netherlands (1988-98) with meningeal signs. Model inputs included probabilities of meningitis and adverse outcome, QALYs for years lived with long-term sequelae, and costs of tests and treatments. Mean outcome measures were costs and effects of diagnostic and therapeutic interventions in children suspected of bacterial meningitis, key determinants of the model outcomes, and evaluation of alternative diagnostic strategies and two vaccination programs in an analysis. RESULTS: The population comprised 99 children with bacterial meningitis (adverse outcome in 10), 36 with serious other bacterial infections, and 225 with self-limiting diseases. Key determinants were the risk of bacterial meningitis or sequelae, costs of treatment, and long-term morbidity. Minimizing lumbar punctures and empirical treatments using a diagnostic decision rule, without missing a single case of meningitis, was a dominant strategy to actual practice. Vaccination strategies of Streptococcus pneumoniae and Neisseria meningitidis resulted in our model in incremental cost-utility ratios of 401,965 Euro dollar ([symbol: see text])/QALY and [symbol: see text]22,635/QALY, respectively. CONCLUSIONS: Costs of long-term morbidity of bacterial meningitis largely outweigh diagnostic and treatment costs. Modeling interventions in children at risk of bacterial meningitis should include long-term consequences in terms of costs and QALYs.

Child, Preschool↗

Cardiovascular risk factors and increased carotid intima-media thickness in healthy young adults: the Atherosclerosis Risk in Young Adults (ARYA) Study.

BACKGROUND: The relation between cardiovascular risk factors and extent of atherosclerosis in middle-aged and elderly populations is well established. Autopsy studies have suggested that similar associations may be present at a young age. We evaluated the relationship between conventional risk factors and increased carotid intima-media thickness (CIMT) in 750 healthy young adults, aged 27 to 30 years. METHODS: All participants completed a questionnaire on cardiovascular risk factors, had a fasting blood sample drawn, and underwent an ultrasonographic examination of both common carotid arteries to assess common CIMT (CCIMT). RESULTS: Age (11.2 micro m/SD), body mass index (10.3 micro m/SD), pulse pressure (5.0 micro m/SD), sex (4.8 micro m/SD), and low-density lipoprotein cholesterol level (4.3 micro m/SD) were independent determinants of increased CCIMT in young adults (R2 = 0.36). Total pack-years of smoking, adjusted for age and sex, showed a linear trend with increased CCIMT (P =.02), which attenuated after further adjustment for body mass index. Common CIMT increased gradually and significantly with the number of cardiovascular risk factors present. The estimated absolute risk, based on the Framingham risk function, for development of coronary heart disease within 20 years was 2.5 times higher in individuals with mean CCIMT in the highest quartile compared with those in the lowest quartile of the distribution. CONCLUSIONS: An unfavorable cardiovascular risk profile is associated with a marked increase in CCIMT in young adulthood. Efforts to change modifiable risk factors early in life may retard atherosclerosis development and hence delay the onset of clinical cardiovascular disease later in life.

Adult↗

Determinants of daily insulin use in Type 1 diabetes.

OBJECTIVE: Insulin need for a given degree of glucose control varies markedly among individuals. We examined which factors determine daily insulin use in patients with Type 1 diabetes. METHODS: A cross-sectional study was performed in 416 patients. Clinical parameters, medication use, physical activity, smoking, alcohol consumption, and laboratory parameters were determined. RESULTS: Body mass index and waist circumference were positively related to daily insulin use (2.3 U/kg/m(2), 95% CI=1.9-2.7 and 0.8 U/cm, 95% CI=0.6-0.9, adjusted for age and sex). Age, female sex, and duration of diabetes were inversely related to daily insulin dose. There was an increase of 3.6 U of insulin per mmol/l triglycerides (95% CI=1.04-6.2) and a decrease of 5.9 U of insulin per mmol/l high-density lipoprotein cholesterol (95% CI=-10.0 to -1.8), adjusted for age, sex, and weight. For blood pressure-lowering drugs, the strongest relation was found for thiazide diuretics (difference of 7.1 U insulin/day, 95% CI=0.2-14.2, adjusted for age, sex, and weight). The use of an insulin pump and physical activity were related to lower daily insulin need: -8.7 U/day (95% CI=-11.8 to -5.5) and -1.7 U/day per activity score unit (95% CI=-3.2 to -0.2), respectively, adjusted for age, sex, and weight. Smoking was related to an increased need of 5.3 U/day (95% CI=1.5-9.0), adjusted for age, sex, and weight. CONCLUSIONS: Our results show that components of the metabolic syndrome are positively related to daily insulin use. Also, decreased physical activity, smoking, and the use of blood pressure-lowering drugs, which influence insulin sensitivity, are associated with an increased insulin need. These findings suggest that the presence of insulin resistance in Type 1 diabetes or "double diabetes" plays a key role in determining daily insulin need.

Adolescent↗

A randomized, placebo-controlled trial on the effects of soy protein containing isoflavones on quality of life in postmenopausal women.

OBJECTIVE: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life (QoL). A number of trials with hormone therapy showed beneficial effects of the intervention on parameters of quality of life. However, because of known or suspected serious side-effects of conventional hormone therapy there is a need for alternatives. DESIGN: We conducted a double-blind randomized placebo-controlled trial with soy protein, containing 52 mg genistein, 41 mg daidzein, and 6 mg glycitein (aglycone weights), or milk protein (placebo) daily for 1 year. For this trial, we recruited 202 postmenopausal women aged 60 to 75 years. RESULTS: At baseline and at final visit, participants filled in the Short Form of 36 questions (SF-36), the Questionnaire on Life Satisfaction Modules (QLS(M)), and the Geriatric Depression Scale (GDS). For the placebo group scores on all dimensions of the SF-36 and the QLS(M) decreased during the intervention year, except for the dimension "role limitations caused by physical problems." The soy group showed increases on two dimensions of the SF-36 ("social functioning" and "role limitations caused by physical problems") and on one dimension of the QLS(M). There were however no statistically significant differences in changes of scores between the two intervention groups. For the GDS similarly, no significant differences were found between the groups. CONCLUSIONS: In conclusion, the findings in this randomized trial do not support the presence of a marked effect of soy protein substitution on quality of life (health status, life satisfaction, and depression) in elderly postmenopausal women.

Aged↗

Factor V Leiden mutation accelerates the onset of natural menopause.

OBJECTIVE: Smoking is consistently associated with a younger age for menopause. Although this may be because of the direct toxic effects of tobacco smoke on follicles, we hypothesize that there may also be a relationship between smoking and a vascular origin of early menopausal onset. Several lifestyle factors have been investigated, but never factors of the clotting cascade. The objective of this study, then, was to determine the effect of factor V Leiden mutation and smoking with respect to age at menopause. DESIGN: Data were used from a subset of 373 postmenopausal participants of a Dutch population-based cohort, born between 1911 and 1925. All women had experienced natural menopause, without use of hormone replacement therapy. RESULTS: Female carriers of the factor V Leiden mutation (n = 14) reported the onset of menopause at an earlier age than noncarriers (n = 359; difference, 3.1 years; 95% CI: 0.3, 5.9). Smoker carriers (n = 5) were 4.3 years younger at menopause than smoker noncarriers (n = 92; 95% CI: 0.9,7.6). In nonsmokers, this relationship was less strong. CONCLUSIONS: We found that the factor V Leiden mutation was related, but not statistically significant, to an earlier age at menopause; smoking possibly enhances this effect. The mutation can be one of the genetic determinants of menopausal age operating through a vascular mechanism.

Factor V↗

Caloric restriction reduces age at menopause: the effect of the 1944-1945 Dutch famine.

OBJECTIVE: To assess the effect of caloric restriction, as endured during the 1944-1945 Dutch famine, on the age at which natural menopause occurs and to identify specific vulnerable age periods in which caloric restriction has the largest effect. DESIGN: This was a population-based cohort study conducted in Utrecht, the Netherlands. Between 1983 and 1986, 9,471 women aged 40 to 73 years at the time of interview were classified regarding their exposure to the famine. Age at natural menopause was obtained from all available data, retrospectively as well as prospectively. We estimated differences in mean age at natural menopause between famine exposure categories (not, moderately, and severely exposed), with adjustment for smoking, parity, socioeconomic status, body mass index, age at menarche, and year of birth. RESULTS: Women experienced natural menopause on average 0.36 years earlier (95% CI: -0.60, -0.11) when severely exposed to the famine and 0.06 years earlier (95% CI: -0.22, 0.09) when moderately exposed compared with the unexposed women. This effect was particularly pronounced in those severely exposed from 2 to 6 years of age: -1.83 years (95% CI: -3.03, -0.63). CONCLUSIONS: Our findings suggest that caloric restriction decreases age at natural menopause. Early childhood seems to be a particularly sensitive age period for this effect.

Adult↗

Rise and fall of hormone therapy in postmenopausal women with cardiovascular disease.

Whereas observational data for postmenopausal women using hormone therapy (HT) have shown a protective effect against cardiovascular disease, prospective, randomized trials have demonstrated a harmful effect on the vascular system. This study describes the effects of HT on lipids, hemostatic parameters, inflammation, and the vascular wall. Reasons for the different results of observational and experimental studies of HT are postulated. The timing of hormonal supplementation seems crucial. Used chronically, HT has no harmful effects; however, first-time use of HT after a recent cardiovascular event results in an early increase in adverse cardiovascular events. In most observational studies, women started HT for postmenopausal symptoms, whereas in experimental studies, women started HT 10 to 20 years or longer after menopause. Cumulative evidence supports the hypothesis that HT has more effect in maintaining vascular health than in alleviating endothelial dysfunction. HT has not proven beneficial in the long term in women at risk of a cardiovascular event. The interval between menopause and the start of HT plays a crucial role in the effectiveness of HT in the vascular system.

Cardiovascular Diseases↗

Cognitive function across the life course and the menopausal transition in a British birth cohort.

OBJECTIVE: Despite biological plausibility, relationships between menopause and cognitive function are inconsistent. We investigated whether menopause status and menopause age were associated with general cognitive ability, verbal memory, and visual search speed and concentration in a large cohort of women while considering vasomotor and psychological symptoms, previous childhood and adult measures of cognitive function, lifetime socioeconomic circumstances, educational attainment, lifestyle factors, and chronic diseases. DESIGN: A nationally representative British cohort of 1261 women born in March 1946 and all aged 53 years at cognitive testing, with prospective information on previous cognitive function, menopausal characteristics, and potential confounders. RESULTS: There was only weak evidence of the effect of natural menopause on cognitive function and no evidence of any effects of hormone therapy use or hysterectomy status. There was a trend across the phases of the natural menopausal transition (pre-, peri-, and postmenopause) for the National Adult Reading Test (P = 0.005) and search speed and concentration (P = 0.042), with postmenopausal women having the lowest cognitive function, but there was no trend in verbal memory. Variation in vasomotor and psychological symptoms did not explain these trends. In postmenopausal women, there was a positive trend across menopause age for verbal memory (P = 0.004) and a weak positive trend for the National Adult Reading Test (P = 0.052), with women who reached menopause later having higher cognitive function. Previous cognitive function generally explained the associations, which were further weakened by adjusting for socioeconomic and educational confounders. One exception was the association between the natural menopause transition and search speed and concentration, which remained after adjustment for these factors. CONCLUSION: Menopause adversely affects cognitive function, but this effect may be largely explained by premenopausal cognitive function. These findings suggest that common environmental or genetic factors, operating through long-term or lifelong hormonal mechanisms, may influence the timing of natural menopause and lifetime cognitive function.

Age Factors↗

Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis.

OBJECTIVE: Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause. DESIGN: A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking. RESULTS: The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01). CONCLUSIONS: Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.

Age Factors↗

Fat mass rather than muscle strength is the major determinant of physical function and disability in postmenopausal women younger than 75 years of age.

OBJECTIVE: Few studies have investigated the relationships between body composition, functional ability, and age-related disability in postmenopausal women. We investigated the relative role of fat mass, lean mass, and muscle strength in the development of disability in a group of healthy postmenopausal women younger than 75 years. DESIGN: We performed a cross-sectional study among 396 independently living women aged 56-73 years, randomly selected between 8 and 30 years after menopause. Lean mass and fat mass were assessed by dual-energy x-ray absorptiometry. Muscle strength (grip and leg extensors) was assessed using dynamometry. Functional ability was estimated by Physical Performance Score, physical activity during the preceding year, and impairment in activities of daily living. RESULTS: Of the participants, 43.7 % were overweight (25 > or = BMI < 30 kg/m2), and 17.7% were obese (BM I > or = 30 kg/m2). Higher muscle strength was observed with increasing lean body mass, and participants with higher muscle strength scored better in the physical performance score and activities of daily living. Higher fat mass was significantly associated with a lower physical performance score, lower physical activity, and a higher frequency of disability. Increasing fat mass was associated with increasing lean mass and decreasing lean/fat ratio. The increase in lean mass and muscle strength associated with higher fat mass was mainly localized in the legs. CONCLUSIONS: Our results support the role of fat mass as the primary risk marker for disability, which might later accelerate by the age-related decrease in lean mass and the development of sarcopenia after the age of 75 years.

Absorptiometry, Photon↗