The Glu318Gly substitution in presenilin 1 is not causally related to Alzheimer disease.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
A Hofman
Publications and source records attributed to A Hofman.
Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study.
BACKGROUND: Epidemiologic studies have shown dietary antioxidants to be inversely correlated with ischemic heart disease. OBJECTIVE: We investigated whether dietary beta-carotene, vitamin C, and vitamin E were related to the risk of myocardial infarction (MI) in an elderly population. DESIGN: The study sample consisted of 4802 participants of the Rotterdam Study aged 55-95 y who were free of MI at baseline and for whom dietary data assessed by a semiquantitative food frequency questionnaire were available. During a 4-y follow-up period, 124 subjects had an MI. The association between energy-adjusted beta-carotene, vitamin C, and vitamin E intakes and risk of MI was examined by multivariate logistic regression. RESULTS: Risk of MI for the highest compared with the lowest tertile of beta-carotene intake was 0.55 (95% CI: 0.34, 0.83; P for trend = 0.013), adjusted for age, sex, body mass index, pack-years, income, education, alcohol intake, energy-adjusted intakes of vitamin C and E, and use of antioxidative vitamin supplements. When beta-carotene intakes from supplements were considered, the inverse relation with risk of MI was slightly more pronounced. Stratification by smoking status indicated that the association was most evident in current and former smokers. No association with risk of MI was observed for dietary vitamin C and vitamin E. CONCLUSION: The results of this observational study in the elderly population of the Rotterdam Study support the hypothesis that high dietary beta-carotene intakes may protect against cardiovascular disease. We did not observe an association between vitamin C or vitamin E and MI.
Aged↗
Serum ferritin and risk of myocardial infarction in the elderly: the Rotterdam Study.
BACKGROUND: Elevated body iron stores have been suggested to be a risk factor for ischemic heart disease. OBJECTIVE: We examined whether elevated serum ferritin concentrations, other indicators of iron status, and dietary iron affected the incidence of myocardial infarction (MI) in an elderly population. DESIGN: A nested, case-control study of 60 patients who had their first MI and 112 age- and sex-matched control subjects embedded in the population-based cohort of the Rotterdam Study. RESULTS: The age- and sex-adjusted risk of MI for subjects with serum ferritin concentrations > or = 200 microg/L was 1.82 (95% CI: 0.90, 3.69; P = 0.096). The odds ratio (OR) was 1.26 (95% CI: 0.98, 1.64; P = 0.078) for the highest tertile of serum ferritin and was only slightly altered in a multivariate model. Risk of MI associated with the highest tertile of ferritin was most evident in current or former smokers (OR: 1.68; 95% CI: 1.17, 2.47; P for trend = 0.008) and in subjects with hypercholesterolemia (OR: 1.43; 95% CI: 0.99, 2.11; P for trend = 0.056) or diabetes (OR: 2.41; 95% CI: 1.12, 7.67; P for trend = 0.027). No association with risk of MI was observed for tertiles of serum iron, serum transferrin, or total dietary iron. For dietary heme iron, risk of MI was significantly increased in a multivariate model in which dietary energy, fat, saturated fat, and cholesterol were adjusted for (OR: 4.01; 95% CI: 1.17, 15.87; P for trend = 0.031). CONCLUSION: In the presence of other risk factors, serum ferritin may adversely affect ischemic heart disease risk in the elderly.
Aged↗
Selecting subjects for ultrasonographic screening for aneurysms of the abdominal aorta: four different strategies.
BACKGROUND: We studied whether the effectiveness of ultrasound screening for abdominal aortic aneurysms could be increased by preselecting high-risk subjects, based on the presence of risk indicators for the disease. METHODS: In a population-based screening programme for abdominal aortic aneurysms among 5328 subjects living in Rotterdam, The Netherlands, we studied four different strategies to select subjects for ultrasound screening of the abdominal aorta, based on risk indicators for abdominal aortic aneurysm disease. Risk indicators used in each strategy were entered in a logistic regression model to predict the probability of an individual having an abdominal aortic aneurysm. Using several cutoff values for the probability of a subject having an aneurysm for each strategy, we estimated the proportion of subjects that should be referred for ultrasound screening and the proportion of aneurysms that would be diagnosed by each strategy (sensitivity). RESULTS: When a probability of 1.5% of having an aneurysm is chosen as the cutoff point above which ultrasound screening is indicated, the proportion of subjects that would be referred for screening ranged from 36% (first strategy) to approximately 50% (other strategies), while 80% (first strategy) to approximately 94% (other three strategies) of all aneurysms would be detected. CONCLUSION: Effectiveness in screening for abdominal aortic aneurysms can be increased by selecting subjects by means of a short medical questionnaire, filled out by the screening candidates, including questions on medical history.
Aged↗
Blood pressure and risk of myocardial infarction in elderly men and women: the Rotterdam study.
OBJECTIVE: To study the association between blood pressure and risk of myocardial infarction in elderly subjects. DESIGN: Prospective cohort study. SETTING: The Rotterdam Study, a Dutch population-based study. PARTICIPANTS: 6004 men and women aged > or = 55 years. MAIN OUTCOME MEASURES: Fatal or non-fatal myocardial infarction (n = 190) during a 4-year follow-up. RESULTS: After excluding participants using blood pressure-lowering medication and participants with a history of myocardial infarction, increasing levels of systolic blood pressure (SBP) were associated with increasing risk of first myocardial infarction (P for trend < 0.0001). The relative risk (RR) for an SBP of 160 mmHg or higher was 5.7 (95% confidence interval (CI) 1.9-17.1) compared with an SBP below 120 mmHg. Increasing diastolic blood pressure (DBP) was also associated with increasing risk of first myocardial infarction, with the RR reaching 2.5 (95% CI 1.4-4.5) in subjects with values of 80-90 mmHg compared with values below 70 mmHg (P for trend < 0.05). Analyses in subjects aged 70 years and over showed that the positive associations between SBP and DBP and risk of first myocardial infarction remained at older age. CONCLUSION: These findings in a relatively healthy cohort of elderly subjects do not provide evidence for a J- or U-shaped relation between SBP and DBP and risk of first myocardial infarction. They suggest that the risk of first myocardial infarction increases with increasing level of systolic and diastolic blood pressure and that this relationship persists into older age.
Aged↗
N-acetyltransferase-2 polymorphism in Parkinson's disease: the Rotterdam study.
The N-acetyltransferase-2 gene (NAT-2) has been associated with Parkinson's disease. The genotype associated with slow acetylation has been reported to be increased in patients with Parkinson's disease. Three mutant alleles M1, M2, and M3 of NAT-2 were investigated in 80 patients with idiopathic Parkinson's disease and 161 age matched randomly selected controls from a prospective population based cohort study. The allelic frequencies and genotypic distributions in patients were very similar to those found in controls. In controls the frequency of the wild type allele increased significantly with age suggesting that the mutant alleles are associated with an increased risk of mortality. These findings suggest that NAT-2 polymorphism is not a major genetic determinant of idiopathic Parkinson's disease, but may be a determinant of mortality in the general population.
Aged↗
Estrogen use and early onset Alzheimer's disease: a population-based study.
Estrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of residence. Information on estrogen use and other risk factors were, for cases (n=109) and controls (n=119), collected from the next of kin by structured interview. The strength of the association between estrogen use and early onset Alzheimer's disease was studied using conditional logistic regression with adjustment for age and education level. There was an inverse association between estrogen use and early onset Alzheimer's disease (adjusted odds ratio 0.34; 95% confidence interval 0.12-0.94). The study therefore suggests that estrogen use is beneficial to Alzheimer's disease with early onset.
Age Factors↗
Menopausal status and distensibility of the common carotid artery.
Although several studies have shown that exogenous estrogens have beneficial effects on arterial characteristics, the effect of endogenous estrogen on the vascular system is still unknown. In this study, distensibility, an indicator of arterial elasticity, of the common carotid artery was compared in pre- and postmenopausal women. The study comprised 93 premenopausal and 93 postmenopausal women of similar age (range, 43 to 55 years). Women were selected from respondents to a mailed questionnaire about the menopause, which was sent to all women aged 40 to 60 years in the Dutch town of Zoetermeer (n=12 675). Postmenopausal women who were at least 3 years past natural menopause or whose menses had stopped naturally before age 48, were age-matched with premenopausal women with regular menses and without menopausal complaints. The selection aimed at maximizing the contrast in estrogen status between pre- and postmenopausal women of the same age. Distensibility of the carotid artery was measured noninvasively with B-mode ultrasound and a vessel wall movement detector system. Arterial distensibility is expressed as the change in arterial diameter (distension, DeltaD) with the cardiac cycle, adjusted for lumen diameter, pulse pressure, and mean arterial blood pressure. Compared with premenopausal women, postmenopausal women had significantly lower arterial distension (DeltaD 370.5 microm [SE 9.5] versus 397.3 microm [SE 9.6]). These results suggest that the distensibility of the common carotid artery is negatively affected by natural menopause in presumed healthy women.
Adult↗
Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women.
Obesity, the insulin resistance syndrome, and atherosclerosis are closely linked and may all be determinants of an increased acute-phase response. In this study, we examined the relationship of C-reactive protein (CRP) with measures of obesity, variables of the insulin resistance syndrome, and intima-media thickness of the common carotid arteries in 186 healthy, middle-aged women selected from the general population. Associations were assessed by regression analysis. CRP was strongly associated with body mass index (BMI) and waist circumference. CRP was also associated with other variables of the insulin resistance syndrome, including blood pressure, insulin, high density lipoprotein cholesterol, triglycerides, apolipoprotein A1 (inversely), plasminogen activator inhibitor-1 antigen, and tissue-type plasminogen activator antigen. Associations between CRP and the variables of the insulin resistance syndrome disappeared after controlling for BMI but remained significant for plasminogen activator inhibitor-1 antigen only. The association of CRP with common carotid artery intima-media thickness was weak and limited to ever-smokers. BMI explained 29.7% of the variance of CRP, whereas common carotid artery intima-media thickness explained only 3.7%. The results of this population-based study indicate that adiposity is strongly associated with CRP in healthy, middle-aged women. In this population, BMI accounted for the relationship between CRP and other variables of the insulin resistance syndrome. Further studies should determine whether losing weight ameliorates the inflammatory state.
Adult↗
J-shaped relation between blood pressure and stroke in treated hypertensives.
The objective of this study was to investigate the relationship between hypertension and risk of stroke in the elderly. The study was performed within the framework of the Rotterdam Study, a prospective population-based cohort study. The risk of first-ever stroke was associated with hypertension (relative risk, 1.6; 95% CI, 1.2 to 2.0) and with isolated systolic hypertension (relative risk, 1.7; 95% CI, 1.1 to 2.6). We found a continuous increase in stroke incidence with increasing blood pressure in nontreated subjects. In treated subjects, we found a J-shaped relation between blood pressure and the risk of stroke. In the lowest category of diastolic blood pressure, the increase of stroke risk was statistically significant compared with the reference category. Hypertension and isolated systolic hypertension are strong risk factors for stroke in the elderly. The increased stroke risk in the lowest stratum of blood pressure in treated hypertensive patients may indicate that the therapeutic goal of "the lower the better" is not the optimal strategy in the elderly.
Aged↗
Hormone replacement therapy and intima-media thickness of the common carotid artery: the Rotterdam study.
BACKGROUND AND PURPOSE: Observational data suggest that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular disease in healthy postmenopausal women. The mechanisms underlying this protection are not entirely clear but may include inhibition of the atherosclerotic process. METHODS: We studied the association between ever use of HRT and intima-media thickness (IMT) of the common carotid artery in 1103 naturally menopausal women, aged 55 to 80 years, in the Rotterdam Study, a community-based cohort study in a suburban area of Rotterdam, Netherlands. Mean and maximum IMT of the common carotid artery were measured noninvasively with B-mode ultrasound. RESULTS: Ever use of HRT for >/=1 year was associated with a decreased mean and maximum IMT compared with never users (mean IMT, 0.719 mm [SE 0.01] versus 0. 742 mm [SE 0.004], P=0.03; maximum IMT, 0.952 mm [SE 0.015] versus 0. 983 mm [SE 0.006], P=0.04), after adjustment for age, smoking, educational level, systolic blood pressure, and body mass index. No association was found for use <1 year (mean IMT, 0.739 mm [SE 0.013] versus 0.742 mm [SE 0.004], P=0.69; maximum IMT, 0.990 mm [SE 0.019] versus 0.983 mm [SE 0.006], P=0.75). Additional adjustment for diabetes, frequency of visits to healthcare facilities, or total and HDL cholesterol did not change these results. CONCLUSIONS: The findings of this population-based study show that ever use of HRT is associated with a decreased IMT in the common carotid artery in elderly women.
Aged↗
Estrogen receptor polymorphism predicts the onset of natural and surgical menopause.
Age at menopause and risk of hysterectomy have strong genetic components, but the genes involved remain ill defined. We investigated whether genetic variation at the estrogen receptor (ER) gene contributes to the variability in the onset of menopause in 900 postmenopausal women, aged 55-80 yr, of the Rotterdam Study, a population-based cohort study in The Netherlands. Gynecological information was obtained, and if women reported surgical menopause, validation of type and indication of surgery was accomplished by checking medical records. The ER genotypes (PP, Pp, and pp) were assessed by PCR using the PvuII endonuclease. Compared with women carrying the pp genotype, homozygous PP women had a 1.1-yr (P < 0.02) earlier onset of menopause. Furthermore, an allele dose effect was observed, corresponding to a 0.5-yr (P < 0.02) earlier onset of menopause per copy of the P allele. The risk of surgical menopause was 2.4 (95% confidence interval, 1.5-3.8) times higher for women carrying the PP genotype compared to those in the pp group, with the most prominent effect in women who underwent hysterectomy due to fibroids or menorrhagia. We conclude that genetic variations of the ER gene are related to the onset of natural menopause and the risk of surgical menopause, especially hysterectomy.
Aged↗
Cerebral vasomotor reactivity and cerebral white matter lesions in the elderly.
OBJECTIVE: The pathogenesis of white matter lesions is still uncertain, but an ischemic-hypoxic cause has been suggested. Cerebral vasomotor reactivity reflects the compensatory dilatory mechanism of the intracerebral arterioles to a vasodilatory stimulus and provides a more sensitive hemodynamic index than the level of resting flow. METHODS: The authors determined the association between vasomotor reactivity and white matter lesions in 73 consecutive individuals from the Rotterdam Scan Study who also participated in the Rotterdam Study, a large population-based prospective follow-up study of individuals > or =55 years old. Vasomotor reactivity was measured by means of CO2-enhanced transcranial Doppler, and in all individuals axial T1*-, T2*-, and proton density (PD)-weighted MRI scans (1.5 T) were obtained. White matter lesions were scored according to location, size, and number by two independent readers. RESULTS: Vasomotor reactivity was inversely associated with the deep subcortical and total periventricular white matter lesions (OR 0.5, 95% CI 0.3 to 1.1; and OR 0.7, 95% CI 0.4 to 1.1, respectively). A strong association was found between impaired vasomotor reactivity and periventricular white matter lesions adjacent to the lateral ventricular wall (OR 0.6, 95% CI 0.4 to 1.0; p = 0.001). No association was found with periventricular white matter lesions near the frontal and occipital horns. CONCLUSIONS: Our data confirm the association between vasomotor reactivity and white matter lesions and support the hypothesis that some white matter lesions may be associated with hemodynamic ischemic injury to the brain.
Aged↗
Education and the incidence of dementia in a large population-based study: the Rotterdam Study.
We assessed the risk of dementia by educational level in a prospective population-based study. In the Rotterdam Study, 6,827 nondemented participants with known education level were followed for an average of 2.1 years. During this period, 137 new cases of dementia occurred. Low education was associated with higher dementia risk in women but not in men, suggesting that the association is modified by sex. Our data indicate that cross-sectional studies may overrate the association between education and risk of dementia.
Age Distribution↗
Fibrinolytic activity in peripheral atherosclerosis in the elderly.
Increased concentrations of plasminogen activator inhibitor type 1 (PAI-1) and of D-dimer have jointly been found in subjects with cardiovascular disease. To understand this apparent paradox of increased inhibition of fibrinolysis (high PAI-1) combined with increased fibrinolytic activity (high D-dimer), we examined the relation between D-dimer, PAI-1 and the activator of fibrinolysis, tissue type plasminogen activator (t-PA) in subjects with varying severity of peripheral atherosclerosis. In 325 subjects selected from the Rotterdam Study, a cohort of 7983 men and women aged 55 years and over, the ankle to brachial systolic blood pressure ratio, t-PA antigen and activity, PAI-1 antigen and D-dimer were measured. T-PA antigen and t-PA activity were, independent from each other, increased with degree of atherosclerosis; t-PA antigen increased with 3.5 ng/ml (SE 1.7, p = 0.04) and t-PA activity with 0.46 IU/ml (0.20, p = 0.02) per unit decrease in ankle to brachial pressure ratio (i.e. increase in atherosclerosis). PAI-1 antigen was not related to atherosclerosis. More marked atherosclerosis was associated with increased D-dimer, mainly in subgroups with PAI-1 antigen below 50 ng/ml, t-PA antigen below 10 ng/ml, or t-PA activity above 1.5 IU/ml. In contrast to current beliefs, we found that only a fraction of the variation of t-PA antigen was due to the variation in circulating PAI-1 antigen. A slight positive association was observed between t-PA antigen and D-dimer. PAI-1 and t-PA activity were not associated with D-dimer concentration. In conclusion, in subjects with peripheral atherosclerosis PAI-1 antigen is not increased, but low PAI-1 levels (and possibly also low levels of t-PA antigen and high levels of t-PA activity) appear to be required to increase circulating D-dimer. This suggests that increased D-dimer levels in subjects with atherosclerosis do not reflect increased inhibition, but rather reflect increased fibrinolysis.
Aged↗
Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study.
AIMS: To determine the prevalence of heart failure and symptomatic as well as asymptomatic left ventricular systolic dysfunction in the general population. METHODS AND RESULTS: In 5540 participants of the Rotterdam Study (age 68.9+/-8.7 years, 2251 men) aged 55-95 years, the presence of heart failure was determined by assessment of symptoms and signs (shortness of breath. ankle oedema and pulmonary crepitations) and use of heart failure medication. In 2267 subjects (age 65.7+/-7.4 years, 1028 men) fractional shortening was measured. The overall prevalence of heart failure was 3.9% (95% CI 3.0+/-4.7) and did not differ between men and women. The prevalence increased with age, with the exception of the highest age group in men. Fractional shortening was higher in women and did not decrease appreciably with age. The prevalence of left ventricular systolic dysfunction (fractional shortening <=25%) was approximately 2.5 times higher in men (5.5%, 95% CI 4.1-7.0) than in women (2.2%, 95% CI 1.4-3.2). Sixty percent of persons with left ventricular systolic dysfunction had no symptoms or signs of heart failure at all. CONCLUSIONS: The prevalence of heart failure is appreciable and does not differ between men and women. The majority of persons with left ventricular systolic dysfunction can be regarded as having asymptomatic left ventricular systolic dysfunction.
Age Factors↗
Serum caeruloplasmin as a coronary risk factor in the elderly: the Rotterdam Study.
Serum Cu and caeruloplasmin levels have been suggested to be independent risk factors for CHD operating through oxidative modification of LDL. However, given its function as an acute-phase protein, the question has been raised whether an elevated caeruloplasmin level is not merely an indicator of inflammation. In the current study, we investigated whether serum caeruloplasmin was associated with subsequent myocardial infarction, taking into account indices of inflammation. The study population consisted of 210 cases of first myocardial infarction and controls, frequency-matched on age (5-year categories) and sex, selected from the population-based cohort of the Rotterdam Study. Serum caeruloplasmin levels were significantly elevated in cases of myocardial infarction compared with controls (510 (SD 110) v. 470 (SD 100) mg/l; P = 0.007). Risk of myocardial infarction for the highest compared with the lowest quartile of caeruloplasmin was 2.46 (95% CI 1.04, 6.00; Ptrend = 0.043) after adjustment for age, sex, BMI, pack-years smoked, serum cholesterol, systolic blood pressure, and income. The relative risk was most evident in current smokers. Adjustment for C-reactive protein and leucocyte count reduced the excess risk by 33%. This suggests that a substantial part of the observed association between serum caeruloplasmin and CHD may be attributed to inflammation processes rather than to the pro-oxidant activity of caeruloplasmin.
Aged↗
Antiepileptic drug regimens and major congenital abnormalities in the offspring.
To assess the risk of major congenital abnormalities associated with specific antiepileptic drug regimens, a large retrospective cohort study was performed. The study comprised 1,411 children born between 1972 and 1992 in four provinces in The Netherlands who were born to mothers with epilepsy and using antiepileptic drugs during the first trimester of pregnancy, and 2,000 nonepileptic matched controls. We found significantly increased risks of major congenital abnormalities for carbamazepine and valproate monotherapy, with evidence for a significant dose-response relationship for valproate. The risk of major congenital abnormalities was nonsignificantly increased for phenobarbital monotherapy when caffeine comedication was excluded, but a significant increase in risk was found when caffeine was included. Phenytoin monotherapy was not associated with an increased risk of major congenital abnormalities. Regarding polytherapy regimens, increased risks were found for several antiepileptic drug combinations. Clonazepam, in combination with other antiepileptic drugs, showed a significantly increased relative risk. Furthermore, there were significantly increased relative risks for the combination of carbamazepine and valproate and the combination of phenobarbital and caffeine with other antiepileptic drugs. This study shows that most antiepileptic drug regimens were associated with an increased risk of major congenital abnormalities in the offspring, in particular valproate (dose-response relationship) and carbamazepine monotherapy, benzodiazepines in polytherapy, and caffeine comedication in combinations with phenobarbital.
Abnormalities, Drug-Induced↗