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Albert Hofman

Publications and source records attributed to Albert Hofman.

211 records · Page 12Linked to original sources

Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study.

BACKGROUND AND PURPOSE: Silent brain infarcts are commonly seen on magnetic resonance imaging (MRI) both in patients with a first stroke and in healthy elderly persons. These infarcts seem associated with an increased risk of stroke. It is unclear whether risk factors for silent infarcts differ from those for symptomatic stroke. We investigated the prevalence of, and cardiovascular risk factors for, silent brain infarcts. METHODS: The Rotterdam Scan Study is a population-based cohort study among 1077 participants 60 to 90 years of age. Participants underwent cerebral MRI. We assessed cardiovascular risk factors by interview and physical examination. Associations between risk factors and presence of infarcts were analyzed by logistic regression and adjusted for age, sex, and relevant confounders. RESULTS: For 259 participants (24%) 1 or more infarcts on MRI were seen; 217 persons had only silent and 42 had symptomatic infarcts. The prevalence odds ratio (OR) of both silent and symptomatic infarcts increased with age by 8% per year (95% CI, 1.06 to 1.10 and 1.04 to 1.13, respectively). Silent infarcts were more frequent in women (age-adjusted OR, 1.4; 95% CI, 1.0 to 1.8). Hypertension was associated with silent infarcts (age- and sex-adjusted OR, 2.4; 95% CI, 1.7 to 3.3), but diabetes mellitus and smoking were not. CONCLUSIONS: Silent brain infarcts are 5 times as prevalent as symptomatic brain infarcts in the general population. Their prevalence increases with age and seems higher in women. Hypertension is associated with silent infarcts, but other cardiovascular risk factors are not.

Age Factors↗

Stroke is associated with coronary calcification as detected by electron-beam CT: the Rotterdam Coronary Calcification Study.

BACKGROUND AND PURPOSE: Coronary calcification as detected by electron-beam CT measures the atherosclerotic plaque burden and has been reported to predict coronary events. Because atherosclerosis is a generalized process, coronary calcification may also be associated with manifest atherosclerotic disease at other sites of the vascular tree. We examined whether coronary calcification as detected by electron-beam CT is related to the presence of stroke. METHODS: From 1997 onward, subjects were invited to participate in the prospective Rotterdam Coronary Calcification Study and undergo electron-beam CT to detect coronary calcification. The study was embedded in the population-based Rotterdam Study. Calcifications were quantified in a calcium score according to Agatston's method. Calcium scores were available for 2013 subjects (mean age [SD], 71 [5.7] years). Fifty subjects had experienced stroke before scanning. RESULTS: Subjects were 2 times more likely to have experienced stroke when their calcium score was between 101 and 500 (odds ratio [OR], 2.1; 95% CI, 0.9 to 4.7) and 3 times more likely when their calcium score was above 500 (OR, 3.3; 95% CI, 1.5 to 7.2), compared with subjects in the lowest calcium score category (0 to 100). Additional adjustment for cardiovascular risk factors did not materially alter the risk estimates. CONCLUSIONS: In this population-based study, a markedly graded association was found between coronary calcification and stroke. The results suggest that coronary calcification as detected by electron-beam CT may be useful to identify subjects at high risk of stroke.

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Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study.

OBJECTIVE: The associations of vitamin B(12), folate, and homocysteine with depression were examined in a population-based study. METHOD: The authors screened 3,884 elderly people for depressive symptoms. Subjects with positive screening results had psychiatric workups. Folate, vitamin B(12), and homocysteine blood levels were compared in 278 persons with depressive symptoms, including 112 with depressive disorders, and 416 randomly selected reference subjects. Adjustments were made for age, gender, cardiovascular disease, and functional disability. RESULTS: Hyperhomocysteinemia, vitamin B(12) deficiency, and to a lesser extent, folate deficiency were all related to depressive disorders. For folate deficiency and hyperhomocysteinemia, the association with depressive disorders was substantially reduced after adjustment for functional disability and cardiovascular disease, but for vitamin B(12) this appeared independent. CONCLUSIONS: The association of vitamin B(12) and folate with depressive disorders may have different underlying mechanisms. Vitamin B(12) may be causally related to depression, whereas the relation with folate is due to physical comorbidity.

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Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study.

In both men and women, circulating androgen levels decline with advancing age. Until now, results of several small studies on the relationship between endogenous androgen levels and atherosclerosis have been inconsistent. In the population-based Rotterdam Study, we investigated the association of levels of dehydroepiandrosterone sulfate (DHEAS) and total and bioavailable testosterone with aortic atherosclerosis among 1,032 nonsmoking men and women aged 55 yr and over. Aortic atherosclerosis was assessed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. Relative to men with levels of total and bioavailable testosterone in the lowest tertile, men with levels of these hormones in the highest tertile had age-adjusted relative risks of 0.4 [95% confidence interval (CI), 0.2-0.9] and 0.2 (CI, 0.1-0.7), respectively, for the presence of severe aortic atherosclerosis. The corresponding relative risks for women were 3.7 (CI, 1.2-11.6) and 2.3 (CI, 0.7-7.8). Additional adjustment for cardiovascular disease risk factors did not materially affect the results in men, whereas in women the associations diluted. Men with levels of total and bioavailable testosterone in subsequent tertiles were also protected against progression of aortic atherosclerosis measured after 6.5 yr (SD +/- 0.5 yr) of follow-up (P for trend = 0.02). No clear association between levels of DHEAS and presence of severe aortic atherosclerosis was found, either in men or in women. In men, a protective effect of higher levels of DHEAS against progression of aortic atherosclerosis was suggested, but the corresponding test for trend did not reach statistical significance. In conclusion, we found an independent inverse association between levels of testosterone and aortic atherosclerosis in men. In women, positive associations between levels of testosterone and aortic atherosclerosis were largely due to adverse cardiovascular disease risk factors.

Age Distribution↗

Osteoporosis in men and women: a story about bone mineral density thresholds and hip fracture risk.

In postmenopausal women, the T score for bone mineral density (BMD) is a well-accepted diagnostic criterion for osteoporosis. It is also used to assess fracture risk. However, it is unclear whether in elderly men similar BMD thresholds should be used. Different hypotheses have been proposed for the relation of BMD with hip fracture risk in men. In this study, we tested those hypotheses using a mathematical model and we compared the calculated results with observed prospective data from the Rotterdam study. In the model, we combined the observed femoral neck BMD distribution for men and women with previously derived hip fracture risk functions based on age and BMD. For men, we tested different hypotheses for the relation of BMD with hip fracture risk. The relation of BMD with hip fracture risk is similar in men and women (scenario 1) or the relative risk (RR) per standard deviation (SD) decrease of BMD is either larger or smaller in men than in women (scenario 2a and 2b), or, at a similar absolute fracture risk, men have a higher BMD (scenario 3). In the prospective data, men with a hip fracture had an average BMD that was 0.070 g/cm2 higher than women with a hip fracture. The calculated results from the first scenario were consistent with those data and were also consistent with the observed hip fracture incidence and the observed female-to-male (F/M) risk ratio (1.7). When the RR for each SD decrease of BMD was assumed to be either larger or smaller in men than in women (second scenario), the calculated average BMD difference in men and women became respectively smaller or larger than observed. When men would have a higher fracture risk at similar BMD levels (third scenario), the calculated total number of hip fractures increased and even exceeded that in women, with an F/M risk ratio of 0.94 in our example. In women, a larger proportion of hip fractures occurs at a T score below -2.5 than in men using the same absolute BMD threshold, but using a male-specific T score largely solves this diagnostic problem. Taken together, the average hip fracture risk in men is much lower than in women but appeared to be similar at the same BMD. Therefore, we propose the use of the same absolute BMD thresholds for decisions about interventions.

Bone Density↗

The incidence of vertebral fractures in men and women: the Rotterdam Study.

Vertebral fractures are considered the most common fractures in osteoporosis. Nevertheless, little is known about the epidemiology of these fractures, especially in men. Therefore, the incidence of vertebral fractures was studied in 3469 men and women from the Rotterdam Study. Spinal radiographs were obtained at baseline and again after a mean follow-up of 6.3 years. The follow-up radiographs were scored for vertebral fractures using the McCloskey-Kanis assessment method. Whenever a vertebral fracture was detected, the radiograph was compared with the baseline radiograph. If this fracture was not already present at baseline, it was considered an incident fracture. The incidence increased strongly with age, ranging from 7.8/1,000 person years (PY) at ages 55-65 years to 19.6/1,000 PY at ages over 75 years for women, and 5.2-9.3/1,000 PY for men, respectively. Analyses repeated in strata of presence or absence of prevalent vertebral fractures showed that both in men and in women, the increase in incidence with age was almost exclusively observed in subjects with one or more prevalent fractures present at baseline. For both genders, the incidence of vertebral fractures doubled per SD decrease in lumbar spine or femoral neck bone mineral density (BMD). This study shows that overall, the incidence of vertebral fractures is higher in women-than in men. In both genders, the incidence increases with age. Furthermore, the presence of a prevalent vertebral fracture and a low BMD are strong independent predictors of incident vertebral fractures in men and women.

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Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants.

BACKGROUND: Several case reports associated combined use of coumarins and antibacterial drugs with overanticoagulation. Despite the fact that these drugs are frequently prescribed concurrently, there is little quantitative information on the risks of such complications. OBJECTIVE: To study which antibacterial drugs are associated with overanticoagulation during therapy with coumarins. DESIGN: Population-based cohort study in a sample of the Rotterdam Study. SUBJECTS: All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available. METHODS: Patients were followed until an INR >/= 6.0, the end of their treatment, death or end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR >/= 6.0 in relation to concomitant use of an oral anticoagulant and antibacterial drugs after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure. RESULTS: Of the 1,124 patients in the cohort, 351 developed an INR >/= 6.0. The incidence rate was 6.9 per 10,000 treatment days. Sulfamethoxazole combined with trimethoprim most strongly increased the risk of overanticoagulation with an adjusted relative risk of 20.1 (95% CI: 10.7-37.9). Stratification showed that the induction period of overanticoagulation varied between different antibacterial drugs. CONCLUSION: In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, several antibacterial drugs strongly increased the risk of overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of antibacterial drug therapy are warranted to minimize the risk of bleeding complications.

Acenocoumarol↗

Renal function and risk of myocardial infarction in an elderly population: the Rotterdam Study.

BACKGROUND: Renal insufficiency is a risk factor for cardiovascular disease in patients with renal disease or coronary heart disease; however, it is unknown whether renal function is an independent predictor of cardiovascular disease in the general population. METHODS: We investigated whether the level of renal function, estimated by glomerular filtration rate, was associated with the risk of incident myocardial infarction among 4484 apparently healthy subjects in the Rotterdam Study (mean age, 69.6 years). We estimated the glomerular filtration rate by Cockcroft-Gault and abbreviated modification of diet in renal disease equations and used Cox regression analysis to estimate hazard ratios adjusted for cardiovascular risk factors, atherosclerosis, and medication use. RESULTS: During the follow-up period (mean, 8.6 years), 218 subjects (4.9%) had a myocardial infarction. A 10 mL/min per 1.73 m(2) decrease in glomerular filtration rate was associated with a 32% increased risk of myocardial infarction (P<.001). Compared with subjects in the fourth quartile, the multivariate-adjusted hazard ratios for the risk of myocardial infarction increased from 1.64 (95% confidence interval [CI], 1.03-2.59) in the third quartile to 1.94 (95% CI, 1.21-3.10) in the second quartile and 3.06 (95% CI, 1.80-5.19) in the quartile with the lowest glomerular filtration rate estimated by the Cockcroft-Gault equation. Using the abbreviated modification of diet in renal disease equation, the risk estimates for the third to first quartiles were 1.34 (95% CI, 0.89-2.01), 1.66 (95% CI, 1.14-2.49), and 1.90 (95% CI, 1.25-2.90), respectively. CONCLUSIONS: The present study shows that renal function is a graded and independent predictor of the development of myocardial infarction in an elderly population. Early detection of decreased renal function may identify subjects who are at heightened risk of coronary heart disease.

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Association between blood pressure levels over time and brain atrophy in the elderly.

The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood pressure and performed MRI in 1077 nondemented elderly (age 60-90 years). For 513 of these, we had information on a blood pressure level 20 years before. The degree of cortical atrophy was semi-quantitatively scored (range 0-15). In late life, a high (>/=90 mmHg) and low (<65 mmHg) diastolic blood pressure were associated with more cortical atrophy than a diastolic blood pressure level between 65-74 mmHg (adjusted difference 0.60 units (95% confidence interval (CI), 0.18-1.02) and 0.77 units (0.28-1.25), respectively). Persons whose diastolic blood pressure had declined more than 10 mmHg over 20 years had more cortical atrophy than those with stable blood pressure levels (adjusted difference 0.53 units, 0.05-1.02). Both high and declining diastolic blood pressure levels are associated with more global brain atrophy on MRI.

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Cerebral haemodynamics in the elderly: the rotterdam study.

Transcranial Doppler ultrasonography allows the non-invasive assessment of cerebral haemodynamics. Data on the frequency distribution of these parameters in the oldest old are scarce, which makes a distinction between physiological and pathophysiological ageing difficult. We studied the relation between cerebral haemodynamic parameters and age and sex in 1,720 participants of a population-based study by means of transcranial Doppler ultrasonography. The end-diastolic, peak systolic and mean cerebral blood flow velocity, and cerebrovascular CO2 reactivity declined significantly with increasing age up to 90 years (per year -0.6 cm/s; -0.3 cm/s; -0.5 cm/s, and -0.6%/kPa, respectively). The pulsatility index increased with age (per year 0.01). End-diastolic, peak systolic and mean cerebral blood flow velocities were lower in men compared to women (age-adjusted difference 1.6 cm/s; 4.1 cm/s, and 2.5 cm/s, respectively). Cerebrovascular CO2 reactivity was higher in men compared to women. Adjusting for carotid atherosclerosis did not change the observed sex differences. These findings provide insight into physiologic changes of haemodynamics during ageing and may serve as a starting point for investigations on determinants of pathophysiologic changes in cerebral haemodynamics in the elderly.

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How do American stroke risk functions perform in a Western European population?

OBJECTIVES: We evaluated the predictive performance of the stroke risk functions from the Framingham and the Cardiovascular Health Study in a population-based study in The Netherlands. METHODS: We assessed how well the functions could estimate the number of strokes in the Rotterdam Study, and how well they could discriminate between high- and low-risk persons. RESULTS: Both functions predicted the number of stroke cases reasonably well, except in persons with a predicted 5-year risk higher than 5%, where they overestimated the risk. The area under the receiver operator characteristic curve was 0.75 (95% confidence interval, 0.71-0.78) for both functions. CONCLUSIONS: Stroke risk functions developed in US populations predict the number of strokes reasonably well in elderly Western European persons at low or modest risk for stroke. The functions can be a useful tool to discriminate between persons at high or low risk for stroke.

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Apparent and internal validity of a Monte Carlo-Markov model for cardiovascular disease in a cohort follow-up study.

OBJECTIVE: To determine the apparent and internal validity of the Rotterdam Ischemic heart disease & Stroke Computer (RISC) model, a Monte Carlo-Markov model, designed to evaluate the impact of cardiovascular disease (CVD) risk factors and their modification on life expectancy (LE) and cardiovascular disease-free LE (DFLE) in a general population (hereinafter, these will be referred to together as (DF)LE). METHODS: The model is based on data from the Rotterdam Study, a cohort follow-up study of 6871 subjects aged 55 years and older who visited the research center for risk factor assessment at baseline (1990-1993) and completed a follow-up visit 7 years later (original cohort). The transition probabilities and risk factor trends used in the RISC model were based on data from 3501 subjects (the study cohort). To validate the RISC model, the number of simulated CVD events during 7 years' follow-up were compared with the observed number of events in the study cohort and the original cohort, respectively, and simulated (DF)LEs were compared with the (DF)LEs calculated from multistate life tables. RESULTS: Both in the study cohort and in the original cohort, the simulated distribution of CVD events was consistent with the observed number of events (CVD deaths: 7.1% v. 6.6% and 7.4% v. 7.6%, respectively; non-CVD deaths: 11.2% v. 11.5% and 12.9% v. 13.0%, respectively). The distribution of (DF)LEs estimated with the RISC model consistently encompassed the (DF)LEs calculated with multistate life tables. CONCLUSIONS: The simulated events and (DF)LE estimates from the RISC model are consistent with observed data from a cohort follow-up study.

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