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Biomedical subjects

A Hofman

Publications and source records attributed to A Hofman.

At least 199 records · Page 11Linked to original sources

Prevention of suicide by youth health care.

The objective of this study was to examine the effect of freely accessible consultation hours in secondary schools by youth health care departments, on population rates for suicide and parasuicide. To this end, an ecologic case-referent study design was used, with data from the Netherlands Bureau of Statistics, the National Hospital Discharge Register, the High-School Students Study, the youth health care departments in the Netherlands and relevant census. Cases were 137 suicide victims aged 15-19 y and 182 12-18 y old subjects admitted to hospital because of parasuicide and additionally coded as having had surgery as a consequence of the attempted suicide or having a pertinent psychiatric disorder. The relevant census in the regions of the participating youth health care departments served as referents. The High-School Students Study included 4997 students aged 12-18 y of which 303 reported having attempted suicide at least once. In the ecologic case-referent studies the adjusted Odds Ratio for completed suicide in regions with open consultation hours was 0.98 (95% CI 0.69-1.38) and the weighted Odds Ratio for parasuicide was 1.30 (95% CI 0.97-1.75). Analysis of the data of the High-School Students Study resulted in an Odds Ratio of 0.96 (95% CI 0.72-1.26). The overall homogeneous Odds Ratio for (para)suicide in regions with open consultation hours for all three studies was 1.00 (95% CI 0.97-1.04); the heterogeneous Odds Ratio was 1.08 (95% CI 0.95 1.09). This study does not support the hypothesis that regions, where youth health care departments have instituted freely accessible consultation hours in secondary schools, show lower rates of suicide or parasuicide compared to regions where no consultation hours were implemented.

Adolescent↗

The -491 A/T polymorphism in the regulatory region of the apolipoprotein E gene and early-onset Alzheimer's disease.

The -491 polymorphism in the promoter region of the apolipoprotein E gene (APOE) has been suggested to be associated with increased risk for Alzheimer's disease (AD) independent of APOE status. We studied the association between the -491 polymorphism and risk for early-onset Alzheimer's disease in 99 Dutch and 78 Spanish patients. In patients with early-onset AD, we found no consistent relationship with a single allele of the -491 polymorphism. Linkage disequilibrium between the polymorphism and the APOE gene was found which most likely might explain the inconsistent findings.

Age of Onset↗

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

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

Aged↗

G-estimation of causal effects: isolated systolic hypertension and cardiovascular death in the Framingham Heart Study.

Time-dependent covariates are often both confounders and intermediate variables. In the presence of such covariates, standard approaches for adjustment for confounding are biased. The method of G-estimation allows for appropriate adjustment. Previous studies applying the G-estimation method have addressed effects on all-cause mortality rather than on specific causes of death. In the present study, a method to adjust for censoring by competing risks is presented. The authors used the approach to estimate the causal effect of isolated systolic hypertension on cardiovascular mortality in the Framingham Heart Study, with a 10-year follow-up using data from 1956 to 1970. Arterial rigidity is a major determinant of isolated systolic hypertension and may be a confounder of the relation between isolated systolic hypertension and cardiovascular death. Conversely, isolated systolic hypertension may by itself contribute to stiffening of the vessel wall, and arterial rigidity may therefore also be an intermediate variable in the causal pathway from isolated systolic hypertension to cardiovascular death. While controlling for arterial rigidity and other baseline and time-dependent covariates, isolated systolic hypertension decreased the time to cardiovascular death by 45% (95% confidence interval 3-69).

Adult↗

Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study.

BACKGROUND: Previous studies suggested a protective effect of smoking on Alzheimer's disease, but most were case-control studies based on prevalent cases. The findings of prospective studies on the association between smoking and the risk of dementia are inconclusive. METHODS: We did a population-based follow-up study of elderly people who were initially free of dementia. 6870 people aged 55 years and older agreed to take part. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers. During follow-up, we recorded all incident cases of dementia. We used never smokers as the reference category to calculate relative risks of dementia and Alzheimer's disease by Cox proportional hazards regression, after adjustment for age, sex, education, and alcohol intake. We also examined modification of risk by age, sex, and the apolipoprotein E (APOE) genotype. FINDINGS: During mean follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were detected, of which 105 were Alzheimer's disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for Alzheimer's disease in individuals without the APOEepsilon4 allele (4.6 [1.5-14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]). INTERPRETATION: Smoking was associated with a doubling of the risk of dementia and Alzheimer's disease. Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimer's disease.

Age Distribution↗

Serum apolipoprotein E level is not increased in Alzheimer's disease: the Rotterdam study.

The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in Alzheimer patients compared to non-demented controls (0.75 micromol/l (SD 0.35), vs. 0.83 micromol/l (SD 0.40), P < 0.05). This finding is in accordance with lower serum apoE levels as observed in carriers of the APOE*4 allele, who are over-represented in Alzheimer's disease. After adjustment for age, sex, total protein, albumin level, body mass index and the APOE genotype, the difference in serum apoE levels largely disappeared. Our population-based study suggests that the differences in serum apoE level between Alzheimer patients and controls are mainly the result of differences in the distribution of the APOE genotype.

Aged↗

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

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

Aged↗

Risk factors for increased bone loss in an elderly population: the Rotterdam Study.

The association of bone loss with age, sex, and several prevalent and modifiable potential risk factors for osteoporosis was studied in 1,856 men and 2,452 women aged 55 years and over from the Rotterdam Study, a population-based cohort study in the Netherlands. The rate of change in femoral neck bone mineral density was estimated longitudinally between 1990 and 1995, after 2 years of follow-up on average. These rates, adjusted for age and body mass index, were -0.0025 (95% confidence interval -0.0038 to -0.0012) in men and -0.0045 (95% confidence interval -0.0056 to -0.0034) g/cm2/year in women (p=0.03). Bone loss accelerated with age, as seen more clearly in men than in women. Lower body mass index and cigarette smoking were associated with increased bone loss in both men and women. In men, higher calcium intake was associated with lower rates, and disability was associated with borderline significantly higher rates of bone loss (p=0.07). In women, a nonsignificant relation was observed with disability, but not with dietary calcium intake. Alcohol intake was not consistently related to the rate of bone loss in either sex. It is concluded that in elderly people the rate of bone loss is higher in women, progresses with age, and is further determined by several modifiable risk factors, particularly in men.

Absorptiometry, Photon↗

Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95. European Union (EU) Collaborative Study Group of Creutzfeldt-Jakob disease (CJD).

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy. Genetic and iatrogenic forms have been recognised but most are sporadic and of unknown cause. We have studied risk factors for CJD as part of the 1993-95 European Union collaborative studies of CJD in Europe. METHODS: The 405 patients with definite or probable CJD who took part in our study had taken part in population-based studies done between 1993 and 1995 in Belgium, France, Germany, Italy, the Netherlands, and the UK. Data on putative risk factors from these patients were compared with data from 405 controls. FINDINGS: We found evidence for familial aggregation of CJD with dementia due to causes other than CJD (relative risk [RR] 2.26, 95% CI 1.31-3.90). No significant increased risk of CJD in relation to a history of surgery and blood transfusion was shown. There was no evidence for an association between the risk of CJD and the consumption of beef, veal, lamb, cheese, or milk. No association was found with occupational exposure to animals or leather. The few positive findings of the study include increased risk in relation to consumption of raw meat (RR 1.63 [95% CI 1.18-2.23]) and brain (1.68 [1.18-2.39]), frequent exposure to leather products (1.94 [1.13-3.33]), and exposure to fertiliser consisting of hoofs and horns (2.32 [1.38-2.91]). Additional analyses, for example stratification by country and of exposures pre-1985 and post-1985, suggest that these results should be interpreted with great caution. INTERPRETATION: Within the limits of the retrospective design of the study, our findings suggest that genetic factors other than the known CJD mutations may play an important part in CJD. Iatrogenic transmission of disease seems rare in this large population-based sample of patients with CJD. There is little evidence for an association between the risk of CJD and either animal exposure, or consumption of processed bovine meat or milk products for the period studied.

Adult↗

Relation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type Ialpha1, a bone-matrix protein. METHODS: We determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of 1778 postmenopausal women using a polymerase-chain-reaction-based assay. We then related the genotypes to bone mineral density and the occurrence of osteoporotic fractures in these women. RESULTS: As compared with the 1194 women with the SS genotype, the 526 women with the Ss genotype had 2 percent lower bone mineral density at the femoral neck (P=0.003) and the lumbar spine (P=0.02); the 58 women with the ss genotype had reductions of 4 percent at the femoral neck (P= 0.05) and 6 percent at the lumbar spine (P=0.005). These differences increased with age (P=0.01 for modification by age of the effect of COLIA1 on femoral-neck bone density, and P=0.004 for modification of the effect on lumbar-spine bone density). Women with the Ss and ss genotypes were overrepresented among the 111 women who had incident nonvertebral fractures (relative risk per copy of the s allele, 1.5; 95 percent confidence interval, 1.1 to 2.1). CONCLUSIONS: The COLIA1 polymorphism is associated with reduced bone density and predisposes women to osteoporotic fractures.

Age Factors↗

Incidence and risk of dementia. The Rotterdam Study.

To assess age-, sex-, and subtype-specific incidence rates of dementia and to calculate the risk of dementia, the authors performed a large, community-based, prospective cohort study on dementia as part of the Rotterdam Study. Participants were recruited among residents of a suburb of Rotterdam, aged 55 years and older. Baseline examinations took place between 1990 and 1993. The average follow-up was 2.1 years. Screening for dementia followed a three-stage protocol. Medical records of subjects who had died or could not be examined in person were evaluated. Of 7,046 subjects who were nondemented at baseline, 162 developed dementia during 15,135 person-years of follow-up, resulting in an overall incidence rate of 10.7 per 1,000 person-years. From the youngest to the oldest 5-year age category, the incidence rate increased from 0.6 to 97.2 per 1,000 person-years. Only in men did the increase level off after age 85. Overall, the incidence rate per 1,000 person-years was 7.7 for Alzheimer's disease and 1.5 for vascular dementia. Dementia incidence rates and dementia-free Kaplan-Meier survival tables were used to calculate age- and sex-specific cumulative risks of dementia. Although the incidence rates of men and women up to age 85 were similar, the lifetime risk of dementia for 55-year-old women was twice as high as for men (0.33 vs. 0.16), reflecting both the higher life expectancy of women and the higher dementia risk at very old age.

Age Distribution↗

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

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

Age Factors↗

Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study.

OBJECTIVES: To provide risk estimates of dementia and Alzheimer disease as a function of the apolipoprotein E (APOE) genotypes and to assess the proportion of dementia that is attributable to the APOE genotypes. DESIGN: Case-control study nested in a population-based cohort study with a mean (SD) follow-up of 2.1 (0.9) years. SETTING: General population in Rotterdam, the Netherlands. PARTICIPANTS: A total of 134 patients with incident dementia and a random sample of 997 nondemented control subjects. No participant had dementia at baseline. MAIN OUTCOME MEASURES: Odds ratios for dementia and Alzheimer disease, the fraction of dementia attributable to the APOE epsilon4 allele, and the proportion of the variance in age at the onset of dementia explained by the APOE genotypes. RESULTS: Persons with the epsilon4/4 genotype had a more than 10-fold higher risk of dementia (odds ratio, 11.2; 95% confidence interval, 3.6-35.2), and subjects with the epsilon3/4 genotype had a 1.7-fold increased risk of dementia (95% confidence interval, 1.0-2.9) as compared with persons with the epsilon3/3 genotype. The proportion of patients with dementia that is attributable to the epsilon4 allele was estimated to be 20%. The APOE genotypes explained up to 10% of the variance in age at the onset of dementia. The association between the epsilon4 allele and dementia was strongest in the youngest age category and in those with a family history of dementia. CONCLUSIONS: The APOE genotype is an important determinant of the risk of dementia. At a population level, however, other factors than the APOE genotype may play an important role in the cause of dementia.

Aged↗

Genetic risk of primary open-angle glaucoma. Population-based familial aggregation study.

OBJECTIVES: To study familial aggregation of primary open-angle glaucoma in a general population and to determine the absolute and relative risks for first-degree relatives. METHODS: First-degree relatives of patients with glaucoma (n = 48) and control subjects (n = 155) from the population-based Rotterdam Study underwent a standardized examination, including perimetry. MAIN OUTCOME MEASURES: Intraocular pressure, vertical cup-disc ratio; and the presence of glaucoma, defined as a visual field defect with a cup-disc ratio of 0.7 or higher or asymmetry of 0.3 or higher between both eyes. RESULTS: The prevalence of glaucoma was 10.4% in siblings of patients, 1.1% in offspring of patients, 0.7% in siblings of controls, and 0% in offspring of controls. Life-time risk of elevated intraocular pressure in relatives of patients vs relatives of controls was 42.5% vs 6.7%, of enlarged cup-disc ratio was 62.2% vs 16.6%, and of glaucoma was 22.0% vs 2.3%, yielding a risk ratio for glaucoma of 9.2 (95% confidence interval = 1.2-73.9). The population-attributable risk of glaucoma was 16.4%. CONCLUSIONS: In a general population, relatives of patients with glaucoma have a strongly increased risk of glaucoma. Enlarged cup-disc ratio, not intraocular pressure, was the earliest and most prominent feature of familial aggregation. Further studies are needed to disentangle the genetic components of the increased familial risk.

Adult↗

Genetic risk of age-related maculopathy. Population-based familial aggregation study.

OBJECTIVE: To investigate to what extent age-related maculopathy (ARM) is genetically determined. DESIGN AND SETTING: Familial aggregation study based on probands derived from the population-based Rotterdam Study. PARTICIPANTS: First-degree relatives of 87 patients with late ARM, i.e., atrophic or neovascular macular degeneration, were compared with first-degree relatives of 135 control subjects without ARM. MAIN OUTCOME MEASURES: Presence and stage of ARM as diagnosed on fundus transparencies, odds ratio, lifetime risk, risk ratio, and population-attributable risk. RESULTS: Independent of other risk factors, the prevalence of early (odds ratio = 4.8, 95% confidence interval [CI] = 1.8-12.2) and late (odds ratio = 19.8, 95% CI = 3.1-126.0) ARM was significantly higher in relatives of patients with late ARM. The lifetime risk estimate of late ARM was 50% (95% CI = 26%-73%) for relatives of patients vs 12% (95% CI = 2%-16%) for relatives of controls (P < .001), yielding a risk ratio of 4.2 (95% CI = 2.6-6.8). Relatives of patients expressed the various features of ARM at a younger age. The population-attributable risk related to genetic factors was 23%. CONCLUSIONS: First-degree relatives of patients with late ARM developed ARM at an increased rate at a relatively young age. Our findings indicate that approximately one fourth of all late ARM is genetically determined and suggest that genetic susceptibility may play an important role in determining the onset of disease.

Adult↗

Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study.

OBJECTIVE: To study the prevalence and causes of blindness and visual impairment in various age categories of a large population-based study. METHODS: For the study, 6775 subjects aged 55 years or older underwent an extensive ophthalmologic screening examination, including measurements of visual acuity and the visual field and fundus photography. The causes of blindness or visual impairment were determined using all screening information and medical records. RESULTS: The prevalence of blindness, according to World Health Organization criteria, ranged from 0.1% in subjects aged 55 to 64 years to 3.9% in subjects aged 85 years or older; the prevalence of visual impairment ranged from 0.1% to 11.8%. For persons younger than 75 years, myopic degeneration and optic neuropathy were the most important causes of impaired vision. For persons aged 75 years or older, age-related macular degeneration was the major cause of the increased prevalence of blindness, whereas age-related cataract predominantly caused the increased prevalence of visual impairment. CONCLUSIONS: The hierarchy of causes of blindness and visual impairment is highly determined by age. As yet, little can be done to reduce the exponential increase of blindness; however, adequate implementation of surgery to treat cataract could reduce visual impairment by one third. Underuse of ophthalmologic care is a prominent cause of the high frequency of untreated cataracts among the elderly.

Age Factors↗

Descriptive epidemiology of Creutzfeldt-Jakob disease in six European countries, 1993-1995. EU Collaborative Study Group for CJD.

After the occurrence of bovine spongiform encephalopathy (BSE), there has been concern that transmission of BSE to the human population might result in a change in the epidemiological characteristics of Creutzfeldt-Jakob disease (CJD). A collaborative study of CJD in the European Union was performed from 1993 to 1995, to compare data from national registries for CJD in France, Germany, Italy, The Netherlands, Slovakia, and the United Kingdom. Five hundred seventy-five patients with definite or probable CJD died in the study period with an overall annual mortality rate of 0.71 cases per million. The incidence rates for CJD were similar in all participating countries despite variations in postmortem rates, and age-specific incidence rates were also relatively consistent, with the exception of an increased incidence of CJD in patients younger than 39 years of age in the United Kingdom. In relation to etiological subtypes of CJD, 87% of cases were sporadic, 8% genetic, and 5% iatrogenic. Genetic forms of CJD comprised 80% of all cases in Slovakia, and iatrogenic forms of CJD occurred most frequently in France and the United Kingdom. The statistical data reported here do not provide evidence of a causal link between BSE and CJD in Europe as a whole. However, the study has established baseline epidemiological parameters for CJD in participating European countries, which may be important in the assessment of any future change in the characteristics of CJD as a result of the epidemic of BSE.

Adult↗

Apolipoprotein E genotype, atherosclerosis, and cognitive decline: the Rotterdam Study.

The apolipoprotein E4 allele (APOE epsilon 4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOE epsilon 4 and atherosclerosis on cognitive decline are independent. A population-based follow-up study was performed on 838 subjects who were non-demented at baseline. The Mini Mental State Examination (MMSE) score at follow-up was studied as a function of APOE epsilon 4 and atherosclerosis. Mild, non-significant effects on the MMSE score were found for atherosclerosis in the absence of APOE epsilon 4 and for APOE epsilon 4 in the absence of atherosclerosis. APOE epsilon 4 carriers with two or more indicators of atherosclerosis positive, had a significantly lower MMSE score at follow-up (mean difference -0.7 points; 95% confidence interval -1.1 to -0.2) relative to non-APOE epsilon 4 carriers with no evidence of atherosclerosis. Our findings suggest that the consequences of APOE epsilon 4 and atherosclerosis are not independent, and that particularly APOE epsilon 4 carriers with atherosclerosis are at increased risk of cognitive decline.

Aged↗