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Albert Hofman

Publications and source records attributed to Albert Hofman.

At least 163 records · Page 9Linked to original sources
PubMed2003

Thiazide diuretics and the risk for hip fracture.

BACKGROUND: Since most hip fractures are related to osteoporosis, treating accelerated bone loss can be an important strategy to prevent hip fractures. Thiazides have been associated with reduced age-related bone loss by decreasing urinary calcium excretion. OBJECTIVE: To examine the association between dose and duration of thiazide diuretic use and the risk for hip fracture and to study the consequences of discontinuing use. DESIGN: Prospective population-based cohort study. SETTING: The Rotterdam Study. PARTICIPANTS: 7891 individuals 55 years of age and older. MEASUREMENTS: Hip fractures were reported by the general practitioners and verified by trained research assistants. Details of all dispensed drugs were available on a day-to-day basis. Exposure to thiazides was divided into 7 mutually exclusive categories: never use, current use for 1 to 42 days, current use for 43 to 365 days, current use for more than 365 days, discontinuation of use since 1 to 60 days, discontinuation of use since 61 to 120 days, and discontinuation of use since more than 120 days. RESULTS: 281 hip fractures occurred. Relative to nonuse, current use of thiazides for more than 365 days was statistically significantly associated with a lower risk for hip fracture (hazard ratio, 0.46 [95% CI, 0.21 to 0.96]). There was no clear dose dependency. This lower risk disappeared approximately 4 months after thiazide use was discontinued. CONCLUSIONS: Thiazide diuretics protect against hip fracture, but this protective effect disappears within 4 months after use is discontinued.

Age Factors↗
PubMed2003

Mutations in the hemochromatosis gene (HFE), Parkinson's disease and parkinsonism.

Iron overload increases oxidative stress and may lead to neurodegenerative disease like Parkinson's disease (PD). We studied the role of mutations in the hemochromatosis gene HFE in PD and other parkinsonism (non-PD PS) in two population-based series. The first series consisted of 137 patients with PD and 47 with non-PD PS, and the second of 60 patients with PD and 25 with non-PD PS. In the first series, PD patients were significantly more often homozygous for the C282Y mutation than controls (P=0.03). Patients with non-PD PS in both series were more often carriers for the C282Y mutation than controls (P=0.009, P=0.006, respectively). Our data are hampered by small numbers, yet suggest that the C282Y mutation increases the risk of PD and non-PD PS. The rarity of this genotype requires a large series of patients to prove our hypothesis.

Aged↗
PubMed2003

Risk factors for progression of atherosclerosis measured at multiple sites in the arterial tree: the Rotterdam Study.

BACKGROUND AND PURPOSE: Studies investigating determinants of atherosclerotic disease progression are relatively rare. Moreover, although atherosclerotic disease can be assessed noninvasively in different vascular beds, previous studies have not considered progression of atherosclerosis at >1 site. The present study was designed to identify risk factors for progression of atherosclerosis measured at multiple sites in the arterial tree. METHODS: The Rotterdam Study is a population-based cohort study of 7983 men and women > or =55 years of age. Carotid plaques and intima-media thickness were assessed by ultrasound, aortic atherosclerosis by x-ray, and lower-extremity atherosclerosis by the ankle-arm index. Data on progression of atherosclerosis over an average period of 6.5 years were available for 3409 participants. Associations of established cardiovascular risk factors with mild, moderate, and severe progression of atherosclerosis were investigated through multinomial regression analysis. RESULTS: Age, smoking, total cholesterol, and systolic blood pressure and/or hypertension were strong, independent predictors of moderate and severe progression of atherosclerosis at multiple sites. Diabetes mellitus predicted only severe progression of atherosclerosis. Associations of sex with progression of atherosclerosis were remarkably modest. CONCLUSIONS: Age, smoking, total cholesterol, and systolic blood pressure and/or hypertension strongly predict progression of extracoronary atherosclerosis in the elderly, but sex remarkably does not. These results emphasize the need for prevention of progression of extracoronary atherosclerotic disease in men and women alike.

Aged↗
PubMed2003

Association of 5' estrogen receptor alpha gene polymorphisms with bone mineral density, vertebral bone area and fracture risk.

This study investigates the influence of genetic variation of the estrogen receptor alpha (ESR1) gene locus on several bone parameters in 2042 individuals of The Rotterdam Study, a prospective population-based cohort study of elderly subjects. We analysed three polymorphic sites in the 5' region of the ESR1 gene; a (TA)(n)-repeat in the promoter region, and molecular haplotypes of the PvuII and XbaI RFLPs in intron 1, and inferred long-range haplotypes (LRH) thereof. We observed only three of the possible four PvuII-XbaI haplotypes in our population. A comparison with other Caucasian populations showed similar haplotype frequencies, while in Asian and African populations these were different. Linkage disequilibrium (LD) analysis between the PvuII-XbaI haplotype and the (TA)(n) repeat showed strong LD between the two sites. Reconstruction of long range haplotypes over the entire 5' region, revealed six frequent LRH. In men, we did not observe an association between the ESR1 polymorphisms studied and bone parameters. In women, we demonstrated an allele dose effect of haplotype "px" (P=0.003) and a low number of (TA)(n) repeats (P=0.008) with decreased lumbar spine bone mineral density (BMD) (4.8% lower BMD in women homozygous for haplotype "px", representing 28% of the population, compared with homozygous non-carriers) and decreased vertebral bone area (2.3% difference between extreme genotypes; P=0.016). Most importantly, we found an increased vertebral fracture risk with evidence for an allele dose effect with an odds ratio of 2.2 (95%CI 1.3-3.5) for haplotype "px", and 2.0 (1.5-3.2) for a low number of (TA)(n) repeats. The ESR1 genotype dependent fracture risk is largely independent of BMD and bone area. Combination of risk alleles at both loci by long-range haplotyping improved the associations slightly, but because of the strong LD between the two polymorphic sites, we were unable to determine if any particular polymorphic site is driving the associations found. We conclude that ESR1 polymorphism in the 5' (promoter) region is associated with vertebral fracture risk, lumbar spine BMD and vertebral bone area in postmenopausal women, but not in men. The molecular mechanism underlying this association needs further study.

Bone Density↗
PubMed2003

The value of C-reactive protein in cardiovascular risk prediction: the Rotterdam Study.

BACKGROUND: Epidemiologic studies have shown that C-reactive protein (CRP) is a risk factor for coronary heart disease. Whether routine measurement of CRP has a role in the prediction of future coronary disease in everyday clinical practice has not yet been investigated. METHODS: Within the Rotterdam Study, a population-based cohort study of 7983 men and women 55 years and older, we conducted a nested case-control study to investigate the value of CRP in coronary disease prediction. Data are based on 157 participants who experienced a myocardial infarction during follow-up and 500 randomly selected controls. High-sensitivity CRP and traditional cardiovascular risk factors were measured at baseline. RESULTS: The age- and sex-adjusted relative risk of myocardial infarction for subjects in the highest quartile of the population distribution of CRP compared with the lowest quartile was 2.0 (95% confidence interval, 1.1-3.4). After additional adjustment for traditional cardiovascular risk factors, the increase in risk largely disappeared (odds ratio, 1.2; 95% confidence interval, 0.6-2.2). Adding CRP to a coronary disease risk function based on risk factors that are routinely assessed in clinical practice or to the Framingham risk function did not improve the area under the receiver operating characteristic curve of these risk functions. Sensitivity and specificity of both risk functions, computed after dichotomizing the estimated disease probabilities using prespecified cutoff points, hardly improved when CRP was added. CONCLUSION: Measurement of CRP in elderly people has no additional value in coronary disease risk prediction when traditional cardiovascular risk factors are known.

Area Under Curve↗
PubMed2003

Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study.

BACKGROUND AND PURPOSE: Silent brain infarcts and white matter lesions are associated with an increased risk of subsequent stroke in minor stroke patients. In healthy elderly people, silent brain infarcts and white matter lesions are common, but little is known about their relevance. We examined the risk of stroke associated with these lesions in the general population. METHODS: The Rotterdam Scan Study is a population-based prospective cohort study among 1077 elderly people. The presence of silent brain infarcts and white matter lesions was scored on cerebral MRI scans obtained from 1995 to 1996. Participants were followed for stroke for on average 4.2 years. We estimated the risk of stroke in relation to presence of brain lesions with Cox proportional hazards regression analysis. RESULTS: Fifty-seven participants (6%) experienced a stroke during follow-up. Participants with silent brain infarcts had a 5 times higher stroke incidence than those without. The presence of silent brain infarcts increased the risk of stroke >3-fold, independently of other stroke risk factors (adjusted hazard ratio 3.9, 95% CI 2.3 to 6.8). People in the upper tertile of the white matter lesion distribution had an increased stroke risk compared with those in the lowest tertile (adjusted hazard ratio for periventricular lesions 4.7, 95% CI 2.0 to 11.2 and for subcortical lesions 3.6, 95% CI 1.4 to 9.2). Silent brain infarcts and severe white matter lesions increased the stroke risk independently of each other. CONCLUSIONS: Elderly people with silent brain infarcts and white matter lesions are at a strongly increased risk of stroke, which could not be explained by the major stroke risk factors.

Aged↗
PubMed2003

Silent brain infarcts and the risk of dementia and cognitive decline.

BACKGROUND: Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline. METHODS: We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions. RESULTS: During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts. CONCLUSIONS: Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions.

Aged↗
PubMed2003

Brain changes with aging: MR spectroscopy at supraventricular plane shows differences between women and men.

PURPOSE: To assess the effect of aging on the proportions of choline (Cho), creatine, and N-acetylaspartate (NAA) in the brains of elderly women and men. MATERIALS AND METHODS: A transverse plane above the ventricle of the brain was mapped with magnetic resonance spectroscopy. Examinations were performed in 1995-1996 with 271 healthy subjects (age range, 60-90 years; mean age, 73 years) and were repeated 4 years later (1999-2000). Student t tests were used for statistical analysis. RESULTS: Difference analysis of the changes in 4 years (paired data) reproduced the decrease in Cho in women only (2.9% per year, P <.001) that had been indicated with intersubject correlation analyses. Decreases in NAA, though significant in both men and women according to age correlation analyses (P <.01 for both), did not reach significance. The resulting sex difference in the Cho/NAA ratio at a mean age of 77 years, while not yet significant at a mean age of 73 years, was especially manifest in the posterior half of the plane analyzed. CONCLUSION: Increasing sex differences in Cho/NAA ratios in a supraventricular plane indicate that brain metabolite levels differ between women and men at advanced age.

Aged↗
PubMed2003

Higher estrogen levels are not associated with larger hippocampi and better memory performance.

BACKGROUND: Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease. OBJECTIVE: To investigate whether higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes on magnetic resonance imaging and better memory performance. DESIGN AND SETTING: Cross-sectional analysis within the Rotterdam Scan Study, a population-based study in the Netherlands of elderly subjects who do not have dementia. PARTICIPANTS: Two hundred ten women and 202 men, aged 60 to 90 years, with plasma levels of total estradiol and, in part, 162 women and 149 men also with levels of bioavailable and free estradiol. MAIN OUTCOME MEASURE: Hippocampal volumes on magnetic resonance imaging and memory performance (delayed recall). RESULTS: Women with higher total estradiol levels had smaller hippocampal volumes and poorer memory performance -0.29 mL (95% confidence interval, -0.57 to -0.00) and -0.4 (95% confidence interval, -1.3 to 0.5) fewer words in delayed recall testing for the highest tertile compared with the lowest tertile. Similar inverse associations were found among bioavailable and free estradiol levels, hippocampal volumes, and memory. In men, no association was observed between estradiol levels and hippocampal volume, but a trend was found for higher levels of total estradiol to be associated with poorer memory performance. CONCLUSION: Our data do not support the hypothesis that higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes and better memory performance.

Age Factors↗
PubMed2003

The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study.

OBJECTIVES: To evaluate the natural course of age-related maculopathy (ARM) and to assess the incidence and absolute risk of its final stage, age-related macular degeneration (AMD). METHODS: In a population-based prospective cohort study of 6418 persons 55 years and older, we studied the incidence and natural course of ARM. Subjects underwent identical examinations, including stereoscopic fundus photography, at baseline and at 2.0 and 6(1/2) years' follow-up. Age-related maculopathy was graded according to the International Classification and Grading System for ARM and AMD, and stratified into 5 exclusive stages. Incidence was expressed in rates and 5-year absolute risks. RESULTS: At follow-up, 47 new cases of AMD were identified, with a ratio of neovascular-atrophic AMD of 1.4:1. The 5-year risk of AMD increased with more severe stages to 28.0% for subjects 55 years and older with indistinct drusen and pigmentary irregularities (stage 3). Age, but not sex, independently increased this risk to a maximum of 42.0% for subjects with stage 3 ARM who were 80 years and older. Individual ARM fundus signs that predicted best the development of AMD were 10 or more large drusen (> or =125 microm) and 10% or more of the grid area covered by drusen. Subjects who developed atrophic AMD showed no significant (P =.25) differences in baseline fundus signs and natural course compared with subjects who developed neovascular AMD. CONCLUSIONS: We provided the absolute risk of AMD as a function of age and early ARM fundus signs, and showed that both are prominent independent risk factors. The progression of ARM stages follows, after the appearance of the first soft drusen, a distinct course at a gradual pace that accelerates with increasing age.

Age Factors↗
PubMed2003

PRNP Val129 homozygosity increases risk for early-onset Alzheimer's disease.

We analyzed the PRNP M129V polymorphism in a Dutch population-based early-onset Alzheimer's disease sample. We observed a significant association between early-onset Alzheimer's disease and homozygosity of M129V (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3; p = 0.02) with the highest risk for V homozygotes (OR, 3.2; 95% CI, 1.4-7.1; p < 0.01). In patients with a positive family history, these risks increased to 2.6 (95% CI, 1.3-5.3; p < 0.01) and 3.5 (95% CI, 1.3-9.3; p = 0.01), respectively.

Adult↗
PubMed2003

Endogenous estradiol and risk of dementia in women and men: the Rotterdam Study.

We determined whether higher endogenous estradiol levels were associated with lower risk of dementia in older men and women not using hormonal replacement therapy, using a case-cohort design within the Rotterdam Study, a population-based follow-up study on chronic diseases, including dementia, in 7983 subjects aged 55 years or older, and ongoing since 1990. The analyses were based on a random subcohort of 508 women and 438 men, and on 76 women and 53 men with incident dementia. Cox proportional hazards models with robustly estimated standard errors showed that in women higher levels of total estradiol were associated with higher risk of dementia (age-adjusted hazard ratio per standard deviation increase 1.38; 95% CI 1.04-1.84). Age-adjusted HR's of Alzheimer's disease and vascular dementia associated with higher levels of total estradiol (per SD increase) were 1.24 (95% CI 0.87-1.76) and 2.19 (95% CI 1.22-3.92), respectively. Similar results were observed for bioavailable estradiol. Additional adjustments for potential confounders did not change the results substantially. In men, no clear association was observed between estradiol levels and risk of dementia or its subtypes. The findings do not support the hypothesis that higher levels of endogenous estradiol reduce risk of dementia, neither in women nor in men.

Aged↗
PubMed2003

Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women.

OBJECTIVE: Genetic influences have been shown to play an important role in the etiology of osteoarthritis (OA), but the genes involved are ill-defined. We studied the association between polymorphisms in the estrogen receptor alpha (ERalpha) gene and the prevalence of radiographic OA of the knee. METHODS: The study group comprised 1,483 men and women from the Rotterdam Study. Direct molecular haplotyping was used to determine the relationship between 2 polymorphisms in the ERalpha gene (the Pvu II and Xba I restriction fragment-length polymorphisms). Radiographs of the knee were evaluated according to the Kellgren/Lawrence (K/L) score, along with separate scores for osteophytosis and joint space narrowing. RESULTS: Three different haplotype alleles were identified: px (54%), PX (34%), and Px (12%). Allele PX was associated with an increased prevalence of radiographic knee OA (K/L score >/=2). The prevalence of radiographic OA was 22% among subjects without allele PX, 24% among those carrying 1 copy, and 35% among subjects carrying 2 copies. The corresponding odds ratios, after adjustment for confounding factors, were 1.3 (95% confidence interval [95% CI] 0.9-1.7) for heterozygotes and 2.2 (95% CI 1.5-3.4) for homozygotes. Separate analyses for men and women showed similar risk estimates. The association appeared to be driven by osteophytosis and is somewhat consistent with the association observed in previous studies of these polymorphisms in relation to OA. CONCLUSION: This study shows that polymorphisms in the ERalpha gene are associated with radiographic OA of the knee, and in particular with osteophytosis, in both elderly men and elderly women.

Age Distribution↗
PubMed2003

Is there a direct association between age-related eye diseases and mortality? The Rotterdam Study.

PURPOSE: To study mortality in subjects with age-related maculopathy (ARM), cataract, or open-angle glaucoma (OAG) in comparison with those without these disorders. DESIGN: Population-based prospective cohort study. PARTICIPANTS: Subjects (n = 6339) aged 55 years and older from the population-based Rotterdam Study for whom complete information on eye disease status was present. MAIN OUTCOME MEASURES: Vital status continuously monitored from 1990 until January 1, 2000. METHODS: The diagnosis of ARM was made according to the International Classification System. Cataract, determined on biomicroscopy, was defined as any sign of nuclear or (sub)cortical cataract, or both, in at least one eye with a visual acuity of 20/40 or less. Aphakia and pseudophakia in at least one eye were classified as operated cataract. Definite OAG was defined as a glaucomatous optic neuropathy combined with a glaucomatous visual field defect. Diagnoses were assessed at baseline. Mortality hazard ratios were computed using Cox proportional hazard regression analysis, adjusted for appropriate confounders (age, gender, smoking status, body mass index, cholesterol level, atherosclerosis, hypertension, history of cardiovascular disease, and diabetes mellitus). RESULTS: The adjusted mortality hazard ratio for subjects with AMD (n = 104) was 0.94 (95% confidence interval [CI], 0.52-1.68), with biomicroscopic cataract (n = 951) was 0.94 (95% CI, 0.74-1.21), with surgical cataract (n = 298) was 1.20 (95% CI, 0.86-1.68), and with definite OAG (n = 44) was 0.39 (95% CI, 0.10-1.55). CONCLUSIONS: Both ARM and cataract are predictors of shorter survival because they have risk factors that also affect mortality. When adjusted for these factors, ARM, cataract, and OAG were themselves not significantly associated with mortality.

Aged↗
PubMed2003

Spatial QRS-T angle predicts cardiac death in a general population.

AIMS: The aim of this study was to assess the prognostic importance of the spatial QRS-T angle for fatal and non-fatal cardiac events. METHODS AND RESULTS: Electrocardiograms (ECGs) were recorded in 6134 men and women aged 55 years and over from the prospective population-based Rotterdam Study. Spatial QRS-T angles were categorized as normal, borderline or abnormal. Using Cox's proportional hazards model, abnormal angles showed increased hazard ratios of cardiac death (age-and sex-adjusted hazard ratio 5.2 (95% CI 4.0-6.8)), non-fatal cardiac events (2.2 (1.5-3.1)), sudden death (5.6 (3.7-8.5)) and total mortality (2.3 (2.0-2.7)). None of the classical cardiovascular and ECG predictors provided larger hazard ratios. After adjustment for these predictors, the association of abnormal spatial QRS-T angles with all fatal study endpoints remained strong, but the association with non-fatal cardiac events disappeared. Computation of Akaike's information criterion showed that the angle contributed significantly to the prediction of all fatal endpoints by classical cardiovascular and ECG predictors. CONCLUSION: The spatial QRS-T angle is a strong and independent predictor of cardiac mortality in the elderly. It is stronger than any of the classical cardiovascular risk factors and ECG risk indicators and provides additional value to them in predicting fatal cardiac events.

Aged↗
PubMed2003

Bone mineral density and the risk of breast cancer: the Rotterdam Study.

Estrogens play an important role in the development of breast cancer, but studies on serum levels of estrogens have shown inconsistent results. Bone mineral density is considered to be a marker for lifetime estrogen exposure. Some studies have suggested that a higher bone mass is associated with an increase in breast cancer risk. We investigated the association between bone mineral density (BMD), as measured at the lumbar spine and femoral neck, and the risk of breast cancer in women age 55 or older in the Rotterdam Study, a population-based cohort study in the Netherlands. Information on baseline lumbar spine and femoral neck BMD, as measured by DEXA (Lunar DPX-L), and cancer incidence was available for 3,107 women. The Rotterdam Cancer Registry provided information on follow-up of incident cancer. After an average follow-up time of 6.5 years, 74 new cases of breast cancer occurred. Z-scores of lumbar spine and femoral neck BMD were divided into tertiles and risk estimates for breast cancer were computed by the Cox proportional hazards model, using the middle tertile as a reference. Breast cancer risk in the upper tertile of lumbar spine BMD was doubled compared to the reference after adjustment for age, body mass index, and age at menopause (hazards ratio = 2.1 [1.1-3.7]), whereas risk estimates for women in the lower tertile did not significantly differ from the reference (hazards ratio = 1.5 [0.8-2.9]). Women with either a low intertrochanteric or femoral neck BMD appeared to have a somewhat decreased breast cancer risk, although this was not statistically significant. The results of this study suggest that in elderly women an association between especially lumbar spine BMD and incident breast cancer exists. Stimulating effects of estrogen on both trabecular bone and mammary cells may be responsible.

Adult↗