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Biomedical subjects

Albert Hofman

Publications and source records attributed to Albert Hofman.

At least 127 records · Page 7Linked to original sources
PubMed2004

Plasma amyloid beta, apolipoprotein E, lacunar infarcts, and white matter lesions.

Lacunar brain infarcts and cerebral white matter lesions are frequently observed on magnetic resonance imaging scans in elderly subjects. These lesions are also frequent in patient with cerebral amyloid angiopathy. We examined whether plasma amyloid beta peptide (Abeta) levels are associated with lacunar infarcts and white matter lesions in the general population, and whether the apolipoprotein E (APOE) genotype modifies these associations. We studied 1,077 participants within the population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia. Cross-sectional associations were analyzed by regression models with adjustments for age, sex, creatinine levels, and hypertension. In APOE epsilon4 carriers, plasma Abeta levels were positively associated with lacunar infarcts and white matter lesions, whereas in noncarriers no associations were observed. Per standard deviation increase in Abeta(1-40) and Abeta(1-42) levels the odds ratios for lacunar infarcts were 1.72 (95% confidence interval [CI] = 1.22-2.43) and 1.93 (95% CI = 1.31-2.85), the periventricular white matter lesion grade increased by 0.32 (95% CI = 0.08-0.57) and 0.29 (95% CI = 0.00-0.57), and the subcortical white matter lesion volume increased by 0.48 ml (95% CI = 0.04-0.91) and 0.24 ml (95% CI = -0.27-0.75). Higher Abeta levels are associated with more lacunar infarcts and white matter lesions in elderly subjects who carry an APOE epsilon4 allele.

Aged↗
PubMed2004

Smoking and Parkinson's disease: systematic review of prospective studies.

We estimated the pooled risk of tobacco smoking for Parkinson's disease (PD). Inclusion criteria included systematic searches of MedLine, PsycLIT, Embase, Current Contents, previously published reviews, examination of cited reference sources, and personal contact and discussion with several investigators expert in the field. Published prospective studies on PD and cigarette smoking. When two or more studies were based on an identical study, the study that principally investigated the relationship or the study that was published last was used. Seven prospective studies were carried out between 1959 and 1997, of which six reported risk estimates. Four cohorts were based on standardised mortality rates, which were exclusively of male. Only one study included risk estimates for both males and females separately. The risk of ever smoker was 0.51 (95% confidence interval, 0.43 to 0.61). There was an obvious protective effect of current smoking in the pooled estimate (relative risk, 0.35; 95% CI, 0.26-0.47). Former smokers had lower risk compared with never smokers (relative risk, 0.66; 95% CI, 0.49-0.88). Although our pooled estimates show that smoking is inversely associated with the risk of PD, the four prospective studies that were based on follow-up of mortality of smokers had many limitations. Further studies evaluating the association between smoking and PD in women are strongly needed.

Adult↗
PubMed2004

Antihypertensive treatment is associated with improved left ventricular geometry: the Rotterdam Study.

PURPOSE: Left ventricular hypertrophy (LVH) increases the risk of cardiovascular disease. We evaluated the association between antihypertensive therapy and echocardiographically determined LVH. METHODS AND RESULTS: The Rotterdam Study is a population-based prospective cohort study among 7983 participants aged 55 years or over. Echocardiography was performed in 2823 participants. The study population consisted of 740 participants with grade 1 hypertension or antihypertensive monotherapy, without heart failure. Of these, 646 had an adequate echocardiogram for analysis of relative wall thickness (RWT) and 642 for left ventricular mass index. Participants were followed from 1 January 1991 until the date of echocardiography, between September 1992 and June 1993. Outcome measures were defined as being in the highest gender-specific quintile of left ventricular mass index and as having a RWT higher than 0.43. A Cox regression model with duration of use of antihypertensives defined as time-dependent covariates was used for data-analysis. Antihypertensive treatment lowered the risk of increased left ventricular mass index (RR 0.6, 95%CI 0.4-0.9). ACE-inhibitors, diuretics and beta-blockers all showed a risk reduction. Use of antihypertensives was also associated, although non-significantly, with a decrease of high RWT (RR 0.8, 95%CI 0.6-1.0). ACE-inhibitors, beta-blockers and calcium antagonists showed similar risk reductions, while diuretics seemed to increase the risk, possibly by reducing left ventricular end diastolic diameter. CONCLUSIONS: The use of antihypertensive drugs is associated with a decreased risk of echocardiographically determined LVH in a population-based setting.

Aged↗
PubMed2004

Apolipoprotein E epsilon4 allele is associated with left ventricular systolic dysfunction.

BACKGROUND: Apolipoprotein (APOE) epsilon4 allele has been associated with cardiac dysfunction in Alzheimer's disease and beta-thalassemia. We investigated the association between APOE genotypes and left ventricular dysfunction in a population of community-dwelling elderly subjects. METHODS: This study was performed in the Rotterdam Study, a population-based prospective cohort study among elderly subjects. For 2206 participants, a baseline echocardiogram and blood specimens for APOE typing were available. Cardiac dysfunction was considered present when fractional shortening was or=65 years. CONCLUSION: The APOE epsilon4 allele is an independent risk factor for cardiac dysfunction in elderly people. Besides well-known effects on atherosclerosis and cholesterol levels, there may be other mechanisms, such as apoptosis, through which this allele exerts negative effects on myocardial performance.

Age Factors↗
PubMed2004

Cholesterol and age-related macular degeneration: is there a link?

PURPOSE: To examine the relation among serum cholesterol, apolipoprotein E genotype (APOE), and the risk of early and late age-related macular degeneration (AMD). DESIGN: The Rotterdam Study, a population based prospective cohort study. METHODS: Serum levels of total and high-density lipoprotein (HDL) cholesterol as well as APOE genotype were determined at baseline. Of 3,944 subjects, 400 were diagnosed with incident early and late AMD after a mean follow-up of 5.2 years. RESULTS: Serum HDL, but not total, cholesterol was associated with an increased risk of AMD (odds ratio/SD, 1.20; 95% confidence interval; 1.06-1.35). The association remained unchanged after adjustment for APOE genotype. When stratifying for APOE genotype, the association was strongest in persons with the e 4 allele; an inverse association seemed to be present for e 2 carriers. CONCLUSION: Elevated HDL but not total cholesterol is associated with an increased risk of AMD. Apolipoprotein E genotype does not explain this association but may be an effect modifier.

Apolipoproteins E↗
PubMed2004

Families and the natural history of blood pressure. A 27-year follow-up study.

BACKGROUND: Previous studies on familial aggregation of blood pressure (BP) have reported data on family history of hypertension. Data on actual parental BP levels and the subsequent natural history of BP in their offspring are scarce. METHODS: In a population-based study with 596 children aged 5 to 19 years, cardiovascular risk factors were measured annually from 1975 through 2002. Parental data were obtained at baseline. Repeated BP measurements were studied as a function of tertiles of age-adjusted BP measured in their parents at baseline. RESULTS: Systolic BP during follow-up was higher in offspring whose parents were both in the highest tertile compared with children whose parents were not in the highest tertile (difference 2.7 mm Hg, 95% confidence interval 0.2 to 5.2). Having both parents in the highest tertile of diastolic BP resulted in a substantially higher diastolic BP ranging from 1.9 mm Hg at age 15 years to 8.5 mm Hg at age 45 years. These differences were adjusted for age, sex, body mass index, total serum cholesterol, smoking habits, and alcohol consumption. CONCLUSIONS: The results of this study indicate that actual parental BP is an important predictor of BP development from childhood into young adulthood. This is important when constituting cardiovascular risk profiles for children and young adults.

Adolescent↗
PubMed2004

The association of Rose questionnaire angina pectoris and coronary calcification in a general population: the Rotterdam Coronary Calcification Study.

PURPOSE: The Rose questionnaire is a standardized method of measuring angina pectoris in general populations. Electron-beam computed tomography (CT) is a non-invasive technique to quantify the amount of coronary calcification. In a population-based study, we investigated the association between Rose questionnaire angina pectoris and coronary calcification. METHODS: The Rotterdam Coronary Calcification Study is embedded in the Rotterdam Study, a population-based study in subjects aged > or = 55 years. Participants of the Rotterdam Coronary Calcification Study underwent an electron-beam CT scan between 1997 and 2000. Coronary calcification was quantified in a calcium score according to Agatston's method. Rose questionnaire angina pectoris was assessed during a home interview. The first 2013 participants were included in the present analyses. RESULTS: In men, the presence of Rose questionnaire angina pectoris was associated with a 12.9-fold (95% confidence interval: 3.8-43.7) increased risk of a calcium score >1000 (reference: calcium score 0-100). The corresponding relative risk in women was 4.8 (2.0-11.3). Similar results were found when we computed sex-specific quartiles of the calcium score. CONCLUSIONS: Rose questionnaire angina pectoris is strongly associated with the amount of coronary calcification. Rose questionnaire angina pectoris corresponds better with the amount of coronary calcification in men than in women.

Aged↗
PubMed2004

Angiotensin-converting enzyme gene polymorphism and common carotid stiffness. The Rotterdam study.

The insertion/deletion (I/D) polymorphism of the ACE gene may be involved in structural arterial changes. Aim of the present study was to assess the relationship between the ACE I/D gene and vessel wall stiffness among older adults. The study was conducted within the Rotterdam study, a population-based cohort study including subjects aged 55 years and older. The II, ID and DD genotypes of the ACE gene were determined in all subjects. The distensibility coefficient (10(-3)/kPa) of the carotid artery and the carotid-femoral pulse wave velocity were measured during the third phase of the Rotterdam study (1997-1999) and were used as measure of arterial stiffness. Data on both carotid stiffness and the ACE genotype were available for 3001 participants. After adjustment for age and gender, subjects with the ID and DD genotype had higher carotid stiffness compared to subjects with II genotype (distensibility coefficient (10(-3)/kPa) 10.24 (95% CI, 10.06-10.43), 10.27 (95% CI, 10.02-10.52), 10.65 (95% CI, 10.37-10.93), respectively (ID versus II genotype, P = 0.017), (DD versus II genotype, P = 0.037)). In stratified analyses, the association was strongest in subjects younger than 70 years. No difference was seen for pulse wave velocity among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with higher common carotid stiffness.

Age Distribution↗
PubMed2004

C-reactive protein and arterial stiffness in older adults: the Rotterdam Study.

Arterial stiffness is one of the characteristics of vascular aging. Increases in pulse pressure, which reflect an increase in the stiffness of the large arteries, are associated with elevated C-reactive protein (CRP) levels. This may suggest a role of inflammation in the development of arterial stiffness. We investigated the relation between measures of arterial stiffness and CRP within the framework of the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. The carotid-femoral pulse wave velocity and the distensibility coefficient of the carotid artery were used as measures of arterial stiffness. Data on both arterial stiffness and CRP were available for 866 participants. In adjusted models, levels of CRP were linearly associated with pulse wave velocity (regression coefficient 0.088, 95% CI 0.006-0.170). Adjusted mean values of pulse wave velocity were significantly different across tertiles of CRP, being higher in the highest tertile of CRP. However, no significant association between CRP and carotid distensibility was observed.

Aged↗
PubMed2004

Risk factors for coronary calcification in older subjects. The Rotterdam Coronary Calcification Study.

AIMS: We examined associations between cardiovascular risk factors and coronary calcification assessed by electron-beam tomography (EBT) in an unselected population of older subjects. METHODS AND RESULTS: The Rotterdam Coronary Calcification Study is a population-based study in subjects > =55 years. Participants underwent EBT scanning. Coronary calcification was quantified according to the Agatston score. Cardiovascular risk factors were assessed 7 years before and concurrently to scanning. We used the first 2013 participants for the present analyses. Risk factors assessed 7 years before scanning were strongly associated with calcium score. Associations with blood pressure and cholesterol attenuated when measured concurrently to scanning. Although the number of risk factors was strongly associated with a high calcium score in asymptomatic subjects, 29% of the men and 15% of the women without risk factors had a high calcium score. CONCLUSIONS: This population-based study in older subjects shows that cardiovascular risk factors are associated with coronary calcification. Associations were stronger for risk factors measured at earlier age. Almost 30% of the men and 15% of the women without risk factors had extensive coronary calcification.

Age Distribution↗
PubMed2004

Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study.

AIMS: To determine the prevalence, incidence rate, lifetime risk and prognosis of heart failure. METHODS AND RESULTS: The Rotterdam Study is a prospective population-based cohort study in 7983 participants aged > or =55. Heart failure was defined according to criteria of the European Society of Cardiology. Prevalence was higher in men and increased with age from 0.9% in subjects aged 55-64 to 17.4% in those aged > or =85. Incidence rate of heart failure was 14.4/1000 person-years (95% CI 13.4-15.5) and was higher in men (17.6/1000 man-years, 95% CI 15.8-19.5) than in women (12.5/1000 woman-years, 95% CI 11.3-13.8). Incidence rate increased with age from 1.4/1000 person-years in those aged 55-59 to 47.4/1000 person-years in those aged > or =90. Lifetime risk was 33% for men and 29% for women at the age of 55. Survival after incident heart failure was 86% at 30 days, 63% at 1 year, 51% at 2 years and 35% at 5 years of follow-up. CONCLUSION: Prevalence and incidence rates of heart failure are high. In individuals aged 55, almost 1 in 3 will develop heart failure during their remaining lifespan. Heart failure continues to be a fatal disease, with only 35% surviving 5 years after the first diagnosis.

Age Distribution↗
PubMed2004

Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects.

AIMS: Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor for cardiac hypertrophy and heart failure, especially in hypertensive subjects. We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects. METHODS AND RESULTS: We investigated 4264 normotensive and 2174 hypertensive participants of the Rotterdam Study, a population based prospective cohort study. All subjects were available for follow-up from 1990 until 2000. Incidence rates (IR) of heart failure in normotensive subjects were the same over all genotype strata (10 per 1000 person-years). In hypertensive subjects, the IR increased with the number of D-alleles present (II: IR=13, ID: IR=18 and DD: IR=20 per 1000 person-years). Hypertensive subjects carrying the II-genotype did not have an increased risk of heart failure compared to normotensive II subjects. However, hypertensive subjects carrying one or two copies of the D-allele did have a significantly increased risk of heart failure (ID: RR: 1.4 (1.1-1.9) and DD: RR: 1.5 (1.2-2.1)). CONCLUSION: Our findings suggest that the ACE I/D polymorphism may play a modifying role in the development of heart failure in hypertensive subjects.

Aged↗
PubMed2004

Comparison of two methodologies to analyze exposure to statins in an observational study on effectiveness.

OBJECTIVE: Estimates of efficacy of drugs from clinical trials may differ from estimates in observational studies. To obtain valid results, the definition of exposure in an observational study is critical. The objective of our study was to compare different exposure definitions for assessing the effectiveness of statins. STUDY DESIGN AND SETTING: The study was performed in the Rotterdam Study, a population-based cohort study that included 7983 subjects of > or =55 years of age. We selected 3806 subjects who received antihyperlipidemic drug treatment (n=179) or had a total cholesterol > or =6.5 mmol/L at baseline. We conducted analyses with two different exposure definitions. RESULTS: Treatment with statins was assessed at baseline. The adjusted relative risk (RR) of myocardial infarction (MI) and stroke was 0.75 (95% confidence interval [CI] 0.41-1.37) and of total mortality was 1.34 (95% CI 0.66-2.74) in subjects treated with statins. We used pharmacy data, which give insight into drug use on a continuous basis. The adjusted RR of MI and stroke after 2 years of cumulative treatment was 0.63 (95% CI 0.34-1.15) and of total mortality was 0.91 (95% CI 0.59-1.39). CONCLUSION: Our results suggest that use of a time-dependent exposure definition is more accurate because estimates of effectiveness were more in agreement with results from randomized controlled trials of statin treatment.

Aged↗
PubMed2004

Is medication use associated with the incidence of early age-related maculopathy? Pooled findings from 3 continents.

OBJECTIVE: To investigate whether there is an association between the use of medication and the incidence of early age-related maculopathy (ARM). DESIGN: Pooled data from 3 prospective, population-based cohort studies. PARTICIPANTS: Subjects without early and late ARM at baseline who participated in the follow-up of the Beaver Dam Eye Study (n = 3012), the Rotterdam Study (n = 3434), and the Blue Mountains Eye Study (n = 2203). METHODS: Stereoscopic color fundus photographs of all participants were graded according to a standardized protocol. At baseline, current use of prescription and over-the-counter medication was assessed by interview, and the drug name was confirmed at the research centers. Procedures and definitions were similar at both baseline and follow-up across the 3 study sites. MAIN OUTCOME MEASURES: Incidence of early ARM, defined as the presence at follow-up of either soft distinct drusen with pigmentary changes or soft indistinct or reticular drusen. RESULTS: In the pooled cohort, 53.3% of participants used at least one of the medications selected for this study. Within a mean period of 5.6 years, a total of 683 subjects developed early ARM. Users of antihypertensive medication in general, and beta-blockers in particular, had a borderline statistically significant increased risk of early ARM (odds ratio [OR] for beta-blockers, 1.3; 95% confidence interval [CI], 1.0-1.6) when adjusted for systolic (or diastolic) blood pressure and other confounders. A protective effect of borderline significance was found among women using hormone replacement therapy (OR, 0.6; 95% CI, 0.4-1.0) and in persons using tricyclic antidepressants (OR, 0.4; 95% CI, 0.2-1.0). In contrast with beta-blockers, the direction and magnitude of the association with hormone replacement therapy and tricyclic antidepressants were inconsistent among the 3 study populations. CONCLUSIONS: Pooled data from 3 population-based studies showed no strong associations between medication use and the incidence of early ARM. Of borderline significance were a slightly increased risk among users of beta-blockers and a reduced risk among users of hormone replacement therapy and users of tricyclic antidepressants. Although beta-blocker use could be a proxy for systemic hypertension, these findings warrant further investigations, preferably including information on the dosage and duration of drug exposure.

Adult↗
PubMed2004

Polymorphisms in the prion protein gene and in the doppel gene increase susceptibility for Creutzfeldt-Jakob disease.

The prion protein gene (PRNP) plays a central role in the origin of Creutzfeldt-Jakob disease (CJD), but there is growing interest in other polymorphisms that may be involved in CJD. Polymorphisms upstream of PRNP that may modulate the prion protein production as well as polymorphisms in the prion-like doppel gene (PRND) have been studied, with inconsistent findings. We investigated the role of a single-nucleotide polymorphism (SNP 1368) located upstream of PRNP and three polymorphisms in PRND (T26M, P56L and T174M) in CJD. The study included a population-based sample of 52 patients with sporadic CJD and 250 controls. We analysed our data as single markers and haplotypes. Further, we conducted a meta-analysis on PRND T174M comparing the data of the four studies conducted to date. For SNP 1368 and PRNP M129V, we found significant evidence for linkage disequilibrium. No evidence was found for a relation of SNP 1368 to CJD independent of PRNP M129V. We further found a significant increased prevalence of M homozygotes at PRND T174M among sporadic CJD patients, when adjusting the analyses for the other genotypes. In the haplotype analyses, the association was strongest for persons homozygous for PRNP 129M and PRND 174M (odds ratio 4.35, 95% confidence interval 1.05-8.09; P=0.04). The meta-analysis on the PRND T174M polymorphism did not show a consistent effect across studies, raising the question as to whether PRND 174M is causally related to CJD, or whether the PRND allele is in linkage disequilibrium with another polymorphism related to CJD.

Adult↗
PubMed2004

Overanticoagulation associated with combined use of lactulose and acenocoumarol or phenprocoumon.

Some medical textbooks on drug interactions take note of the potential interaction between laxatives and coumarin anticoagulants, but epidemiological evidence that this interaction is of practical importance is lacking. We conducted a follow-up study in a large population-based cohort to investigate which laxatives are associated with overanticoagulation during therapy with coumarins. Of the 1124 patients in the cohort, 351 developed an International Normalized Ratio > or = 6.0. The only laxative with a moderate but significantly increased relative risk of overanticoagulation was lactulose (relative risk 3.4, 95% confidence interval 2.2, 5.3). In view of the widespread use of lactulose, especially among the elderly, awareness of this potential drug interaction is required.

Acenocoumarol↗